Skip to main content
SpringerLink
Log in
Book cover

Progress in Cancer Immunotherapy pp 69–138Cite as

Biological Response Modifier in Cancer Immunotherapy

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 909))

Abstract

Biological response modifiers (BRMs) emerge as a lay of new compounds or approaches used in improving cancer immunotherapy. Evidences highlight that cytokines, Toll-like receptor (TLR) signaling, and noncoding RNAs are of crucial roles in modulating antitumor immune response and cancer-related chronic inflammation, and BRMs based on them have been explored. In particular, besides some cytokines like IFN-α and IL-2, several Toll-like receptor (TLR) agonists like BCG, MPL, and imiquimod are also licensed to be used in patients with several malignancies nowadays, and the first artificial small noncoding RNA (microRNA) mimic, MXR34, has entered phase I clinical study against liver cancer, implying their potential application in cancer therapy. According to amounts of original data, this chapter will review the regulatory roles of TLR signaling, some noncoding RNAs, and several key cytokines in cancer and cancer-related immune response, as well as the clinical cases in cancer therapy based on them.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Adams, S. (2009). Toll-like receptor agonists in cancer therapy. Immunotherapy, 1, 949–964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adams, S., Kozhaya, L., Martiniuk, F., Meng, T. C., Chiriboga, L., Liebes, L., Hochman, T., Shuman, N., Axelrod, D., Speyer, J., et al. (2012). Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 18, 6748–6757.

    Article  CAS  Google Scholar 

  • Akdis, M., Burgler, S., Crameri, R., Eiwegger, T., Fujita, H., Gomez, E., Klunker, S., Meyer, N., O’Mahony, L., Palomares, O., et al. (2011). Interleukins, from 1 to 37, and interferon-gamma: Receptors, functions, and roles in diseases. The Journal of Allergy and Clinical Immunology, 127, 701–721.e701–770.

    Article  CAS  PubMed  Google Scholar 

  • Alizadeh, D., Zhang, L., Brown, C. E., Farrukh, O., Jensen, M. C., & Badie, B. (2010). Induction of anti-glioma natural killer cell response following multiple low-dose intracerebral CpG therapy. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 16, 3399–3408.

    Article  CAS  Google Scholar 

  • Amado, T., Schmolka, N., Metwally, H., Silva-Santos, B., & Gomes, A. Q. (2015). Cross-regulation between cytokine and microRNA pathways in T cells. European Journal of Immunology, 45, 1584–1595.

    Article  CAS  PubMed  Google Scholar 

  • Arango Duque, G., & Descoteaux, A. (2014). Macrophage cytokines: Involvement in immunity and infectious diseases. Frontiers in Immunology, 5, 491.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ardolino, M., Hsu, J., & Raulet, D. H. (2015). Cytokine treatment in cancer immunotherapy. Oncotarget, 6, 19346–19347.

    Article  PubMed  PubMed Central  Google Scholar 

  • Arits, A. H., Mosterd, K., Essers, B. A., Spoorenberg, E., Sommer, A., De Rooij, M. J., van Pelt, H. P., Quaedvlieg, P. J., Krekels, G. A., van Neer, P. A., et al. (2013). Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: A single blind, non-inferiority, randomised controlled trial. The Lancet Oncology, 14, 647–654.

    Article  CAS  PubMed  Google Scholar 

  • Arunkumar, N., Liu, C., Hang, H., & Song, W. (2013). Toll-like receptor agonists induce apoptosis in mouse B-cell lymphoma cells by altering NF-kappaB activation. Cellular & Molecular Immunology, 10, 360–372.

    Article  CAS  Google Scholar 

  • Asprodites, N., Zheng, L., Geng, D., Velasco-Gonzalez, C., Sanchez-Perez, L., & Davila, E. (2008). Engagement of Toll-like receptor-2 on cytotoxic T-lymphocytes occurs in vivo and augments antitumor activity. FASEB Journal: Official Publication Federation American Societies for Experimental Biology, 22, 3628–3637.

    Article  CAS  Google Scholar 

  • Babar, I. A., Cheng, C. J., Booth, C. J., Liang, X., Weidhaas, J. B., Saltzman, W. M., & Slack, F. J. (2012). Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma. Proceedings of the National Academy of Sciences of the United States of America, 109, E1695–E1704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bader, A. G., Brown, D., Stoudemire, J., & Lammers, P. (2011). Developing therapeutic microRNAs for cancer. Gene Therapy, 18, 1121–1126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baek, S., Kim, C. S., Kim, S. B., Kim, Y. M., Kwon, S. W., Kim, Y., Kim, H., & Lee, H. (2011). Combination therapy of renal cell carcinoma or breast cancer patients with dendritic cell vaccine and IL-2: Results from a phase I/II trial. Journal of Translational Medicine, 9, 178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bailey, S. R., Nelson, M. H., Himes, R. A., Li, Z., Mehrotra, S., & Paulos, C. M. (2014). Th17 cells in cancer: The ultimate identity crisis. Frontiers in Immunology, 5, 276.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Baird, A. M., Gray, S. G., & O’Byrne, K. J. (2011). IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF. European Journal of Cancer, 47, 1908–1918.

    Article  CAS  PubMed  Google Scholar 

  • Bala, S., Marcos, M., Kodys, K., Csak, T., Catalano, D., Mandrekar, P., & Szabo, G. (2011). Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease. Journal of Biological Chemistry, 286, 1436–1444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ballarin-Gonzalez, B., Ebbesen, M. F., & Howard, K. A. (2014). Polycation-based nanoparticles for RNAi-mediated cancer treatment. Cancer Letters, 352, 66–80.

    Article  CAS  PubMed  Google Scholar 

  • Basith, S., Manavalan, B., Yoo, T. H., Kim, S. G., & Choi, S. (2012). Roles of toll-like receptors in cancer: A double-edged sword for defense and offense. Archives of Pharmacal Research, 35, 1297–1316.

    Article  CAS  PubMed  Google Scholar 

  • bCui, T. X., Kryczek, I., Zhao, L., Zhao, E., Kuick, R., Roh, M. H., Vatan, L., Szeliga, W., Mao, Y., Thomas, D. G., et al. (2013). Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity, 39, 611–621.

    Article  CAS  Google Scholar 

  • Bendigs, S., Salzer, U., Lipford, G. B., Wagner, H., & Heeg, K. (1999). CpG-oligodeoxynucleotides co-stimulate primary T cells in the absence of antigen-presenting cells. European Journal of Immunology, 29, 1209–1218.

    Article  CAS  PubMed  Google Scholar 

  • Blum, J. S., & Saltzman, W. M. (2008). High loading efficiency and tunable release of plasmid DNA encapsulated in submicron particles fabricated from PLGA conjugated with poly-L-lysine. Journal of Controlled Release: Official Journal of the Controlled Release Society, 129, 66–72.

    Article  CAS  Google Scholar 

  • Bolland, D. J., Wood, A. L., Johnston, C. M., Bunting, S. F., Morgan, G., Chakalova, L., Fraser, P. J., & Corcoran, A. E. (2004). Antisense intergenic transcription in V(D)J recombination. Nature Immunology, 5, 630–637.

    Article  CAS  PubMed  Google Scholar 

  • Bouchie, A. (2013). First microRNA mimic enters clinic. Nature Biotechnology, 31, 577.

    Article  CAS  PubMed  Google Scholar 

  • Buchser, W. J., Laskow, T. C., Pavlik, P. J., Lin, H. M., & Lotze, M. T. (2012). Cell-mediated autophagy promotes cancer cell survival. Cancer Research, 72, 2970–2979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calin, G. A., Dumitru, C. D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., Aldler, H., Rattan, S., Keating, M., Rai, K., et al. (2002). Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America, 99, 15524–15529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Capitini, C. M., Chisti, A. A., & Mackall, C. L. (2009). Modulating T‐cell homeostasis with IL‐7: Preclinical and clinical studies. Journal of Internal Medicine, 266, 141–153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caron, G., Duluc, D., Fremaux, I., Jeannin, P., David, C., Gascan, H., & Delneste, Y. (2005). Direct stimulation of human T cells via TLR5 and TLR7/8: Flagellin and R-848 up-regulate proliferation and IFN-gamma production by memory CD4+ T cells. Journal of Immunology (Baltimore, Md.: 1950), 175, 1551–1557.

    Article  CAS  Google Scholar 

  • Carpenter, S., Aiello, D., Atianand, M. K., Ricci, E. P., Gandhi, P., Hall, L. L., Byron, M., Monks, B., Henry-Bezy, M., Lawrence, J. B., et al. (2013). A long noncoding RNA mediates both activation and repression of immune response genes. Science (New York, NY), 341, 789–792.

    Article  CAS  Google Scholar 

  • Chaudhuri, A. A., So, A. Y., Sinha, N., Gibson, W. S., Taganov, K. D., O’Connell, R. M., & Baltimore, D. (2011). MicroRNA-125b potentiates macrophage activation. Journal of Immunology, 187, 5062–5068.

    Article  CAS  Google Scholar 

  • Cheever, M. A. (2008). Twelve immunotherapy drugs that could cure cancers. Immunological Reviews, 222, 357–368.

    Article  CAS  PubMed  Google Scholar 

  • Chen, Y., Zhu, X., Zhang, X., Liu, B., & Huang, L. (2010). Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Molecular Therapy: The Journal of the American Society of Gene Therapy, 18, 1650–1656.

    Article  CAS  Google Scholar 

  • Chen, M. H., Li, W. S., Lue, Y. S., Chu, C. L., Pan, I. H., Ko, C. H., Chen, D. Y., Lin, C. H., Lin, S. H., Chang, C. P., et al. (2013). Clitocybe nuda activates dendritic cells and acts as a DNA vaccine adjuvant. Evidence-Based Complementary Alternative Medicine: eCAM, 2013, 761454.

    PubMed  PubMed Central  Google Scholar 

  • Chen, S., Zhang, Y., Kuzel, T. M., & Zhang, B. (2015). Regulating tumor myeloid-derived suppressor cells by MicroRNAs. Cancer Cell Microenvironment 2, 761454.

    Google Scholar 

  • Cherfils-Vicini, J., Platonova, S., Gillard, M., Laurans, L., Validire, P., Caliandro, R., Magdeleinat, P., Mami-Chouaib, F., Dieu-Nosjean, M. C., Fridman, W. H., et al. (2010). Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance. The Journal of Clinical Investigation, 120, 1285–1297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiffoleau, E., Heslan, J. M., Heslan, M., Louvet, C., Condamine, T., & Cuturi, M. C. (2007). TLR9 ligand enhances proliferation of rat CD4+ T cell and modulates suppressive activity mediated by CD4+ CD25+ T cell. International Immunology, 19, 193–201.

    Article  CAS  PubMed  Google Scholar 

  • Chiou, G. Y., Cherng, J. Y., Hsu, H. S., Wang, M. L., Tsai, C. M., Lu, K. H., Chien, Y., Hung, S. C., Chen, Y. W., Wong, C. I., et al. (2012). Cationic polyurethanes-short branch PEI-mediated delivery of Mir145 inhibited epithelial-mesenchymal transdifferentiation and cancer stem-like properties and in lung adenocarcinoma. Journal of Controlled Release: Official Journal of the Controlled Release Society, 159, 240–250.

    Article  CAS  Google Scholar 

  • Christian, D. A., & Hunter, C. A. (2012). Particle-mediated delivery of cytokines for immunotherapy. Immunotherapy, 4, 425–441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chun-Guang, M., Qi-Man, L., Yu-Yun, Z., Li-Hua, C., Cheng, T., & Jian-De, H. (2014). Successful treatment of giant basal cell carcinoma with topical imiquimod 5% cream with long term follow-up. Indian Journal of Dermatology, 59, 575–578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cobos Jimenez, V., Bradley, E. J., Willemsen, A. M., van Kampen, A. H., Baas, F., & Kootstra, N. A. (2014). Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages. Physiological Genomics, 46, 91–103.

    Article  PubMed  CAS  Google Scholar 

  • Cottalorda, A., Verschelde, C., Marcais, A., Tomkowiak, M., Musette, P., Uematsu, S., Akira, S., Marvel, J., & Bonnefoy-Berard, N. (2006). TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation. European Journal of Immunology, 36, 1684–1693.

    Article  CAS  PubMed  Google Scholar 

  • Croce, M., Orengo, A. M., Azzarone, B., & Ferrini, S. (2012). Immunotherapeutic applications of IL-15. Immunotherapy, 4, 957–969.

    Article  CAS  PubMed  Google Scholar 

  • Croce, M., Rigo, V., & Ferrini, S. (2015). IL-21: A pleiotropic cytokine with potential applications in oncology. Journal of Immunology Research, 2015, 696578.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cubillos-Ruiz, J. R., Baird, J. R., Tesone, A. J., Rutkowski, M. R., Scarlett, U. K., Camposeco-Jacobs, A. L., Anadon-Arnillas, J., Harwood, N. M., Korc, M., Fiering, S. N., et al. (2012). Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer. Cancer Research, 72, 1683–1693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Curtin, J. F., Liu, N., Candolfi, M., Xiong, W., Assi, H., Yagiz, K., Edwards, M. R., Michelsen, K. S., Kroeger, K. M., Liu, C., et al. (2009). HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Medicine, 6, e10.

    Article  PubMed  CAS  Google Scholar 

  • Cutler, A., & Brombacher, F. (2005). Cytokine therapy. Annals of the New York Academy of Sciences, 1056, 16–29.

    Article  CAS  PubMed  Google Scholar 

  • Danielson, L. S., Reavie, L., Coussens, M., Davalos, V., Castillo-Martin, M., Guijarro, M. V., Coffre, M., Cordon-Cardo, C., Aifantis, I., Ibrahim, S., et al. (2015). Limited miR-17-92 overexpression drives hematologic malignancies. Leukemia Research, 39, 335–341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Andrea, M., Ravera, R., Gioia, D., Gariglio, M., & Landolfo, S. (2002). The interferon system: An overview. European Journal of Paediatric Neurology: EJPN: Official Journal European Paediatric Neurology Society, 6(Suppl A), A41–A46; discussion A55-48.

    Article  Google Scholar 

  • de la Rosa, M., Rutz, S., Dorninger, H., & Scheffold, A. (2004). Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. European Journal of Immunology, 34, 2480–2488.

    Article  PubMed  CAS  Google Scholar 

  • de Martimprey, H., Bertrand, J. R., Fusco, A., Santoro, M., Couvreur, P., Vauthier, C., & Malvy, C. (2008). siRNA nanoformulation against the ret/PTC1 junction oncogene is efficient in an in vivo model of papillary thyroid carcinoma. Nucleic Acids Research, 36, e2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de Martimprey, H., Bertrand, J. R., Malvy, C., Couvreur, P., & Vauthier, C. (2010). New core-shell nanoparticles for the intravenous delivery of siRNA to experimental thyroid papillary carcinoma. Pharmaceutical Research, 27, 498–509.

    Article  PubMed  CAS  Google Scholar 

  • de Rosa, F., Fanini, F., Guidoboni, M., Vannini, I., Amadori, D., Ridolfi, R., Ridolfi, L., & Fabbri, M. (2014). MicroRNAs and dendritic cell-based vaccination in melanoma patients. Melanoma Research, 24, 181–189.

    Article  PubMed  CAS  Google Scholar 

  • Della Latta, V., Cecchettini, A., Del Ry, S., & Morales, M. A. (2015). Bleomycin in the setting of lung fibrosis induction: From biological mechanisms to counteractions. Pharmacological Research, 97, 122–130.

    Article  CAS  PubMed  Google Scholar 

  • Deng, G., & Sui, G. (2013). Noncoding RNA in oncogenesis: A new era of identifying key players. International Journal of Molecular Sciences, 14, 18319–18349.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Deng, S., Zhu, S., Qiao, Y., Liu, Y. J., Chen, W., Zhao, G., & Chen, J. (2014). Recent advances in the role of toll-like receptors and TLR agonists in immunotherapy for human glioma. Protein & Cell, 5, 899–911.

    Article  CAS  Google Scholar 

  • Denies, S., Cicchelero, L., Van Audenhove, I., & Sanders, N. N. (2014). Combination of interleukin-12 gene therapy, metronomic cyclophosphamide and DNA cancer vaccination directs all arms of the immune system towards tumor eradication. Journal of Controlled Release: Official Journal of the Controlled Release Society, 187, 175–182.

    Article  CAS  Google Scholar 

  • Desai, S., Laskar, S., & Pandey, B. N. (2013). Autocrine IL-8 and VEGF mediate epithelial-mesenchymal transition and invasiveness via p38/JNK-ATF-2 signalling in A549 lung cancer cells. Cellular Signalling, 25, 1780–1791.

    Article  CAS  PubMed  Google Scholar 

  • Didierlaurent, A., Ferrero, I., Otten, L. A., Dubois, B., Reinhardt, M., Carlsen, H., Blomhoff, R., Akira, S., Kraehenbuhl, J. P., & Sirard, J. C. (2004). Flagellin promotes myeloid differentiation factor 88-dependent development of Th2-type response. Journal of Immunology, 172, 6922–6930.

    Article  CAS  Google Scholar 

  • Dietsch, G. N., Randall, T. D., Gottardo, R., Northfelt, D. W., Ramanathan, R. K., Cohen, P. A., Manjarrez, K. L., Newkirk, M., Bryan, J. K., & Hershberg, R. M. (2015). Late stage cancer patients remain highly responsive to immune activation by the selective TLR8 agonist motolimod (VTX-2337). Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 21, 5445–5452.

    Article  CAS  Google Scholar 

  • Drexler, S. K., & Yazdi, A. S. (2013). Complex roles of inflammasomes in carcinogenesis. Cancer Journal, 19, 468–472.

    Article  CAS  Google Scholar 

  • Eisele, G., Wischhusen, J., Mittelbronn, M., Meyermann, R., Waldhauer, I., Steinle, A., Weller, M., & Friese, M. A. (2006). TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells. Brain: A Journal of Neurology, 129, 2416–2425.

    Article  Google Scholar 

  • El Andaloussi, A., Sonabend, A. M., Han, Y., & Lesniak, M. S. (2006). Stimulation of TLR9 with CpG ODN enhances apoptosis of glioma and prolongs the survival of mice with experimental brain tumors. Glia, 54, 526–535.

    Article  PubMed  Google Scholar 

  • Fabani, M. M., Abreu-Goodger, C., Williams, D., Lyons, P. A., Torres, A. G., Smith, K. G., Enright, A. J., Gait, M. J., & Vigorito, E. (2010). Efficient inhibition of miR-155 function in vivo by peptide nucleic acids. Nucleic Acids Research, 38, 4466–4475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fabbri, M., Paone, A., Calore, F., Galli, R., Gaudio, E., Santhanam, R., Lovat, F., Fadda, P., Mao, C., Nuovo, G. J., et al. (2012). MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proceedings of the National Academy of Sciences of the United States of America, 109, E2110–E2116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang, H., Ang, B., Xu, X., Huang, X., Wu, Y., Sun, Y., Wang, W., Li, N., Cao, X., & Wan, T. (2014). TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells. Cellular & Molecular Immunology, 11, 150–159.

    Article  CAS  Google Scholar 

  • Fernandes, J. V., Cobucci, R. N., Jatoba, C. A., Fernandes, T. A., de Azevedo, J. W., & de Araujo, J. M. (2015). The role of the mediators of inflammation in cancer development. Pathology and Oncology Research, 21, 527–534.

    Article  CAS  PubMed  Google Scholar 

  • Fife, K. H., Meng, T. C., Ferris, D. G., & Liu, P. (2008). Effect of resiquimod 0.01 % gel on lesion healing and viral shedding when applied to genital herpes lesions. Antimicrobial Agents and Chemotherapy, 52, 477–482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finoux, A. L., & Chartrand, P. (2008). Oncogenic and tumour suppressor microRNAs. Medicine Sciences: M/S, 24, 1049–1054.

    Google Scholar 

  • Fitzgerald, K. A., & Caffrey, D. R. (2014). Long noncoding RNAs in innate and adaptive immunity. Current Opinion in Immunology, 26, 140–146.

    Article  CAS  PubMed  Google Scholar 

  • Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S. M., & Maniatis, T. (2003). IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nature Immunology, 4, 491–496.

    Article  CAS  PubMed  Google Scholar 

  • Franks, H. A., Wang, Q., & Patel, P. M. (2012). New anticancer immunotherapies. Anticancer Research, 32, 2439–2453.

    CAS  PubMed  Google Scholar 

  • Gabrilovich, D. I., & Nagaraj, S. (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nature Reviews Immunology, 9, 162–174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gasche, J. A., Hoffmann, J., Boland, C. R., & Goel, A. (2011). Interleukin-6 promotes tumorigenesis by altering DNA methylation in oral cancer cells. International Journal of Cancer, 129, 1053–1063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gelman, A. E., Zhang, J., Choi, Y., & Turka, L. A. (2004). Toll-like receptor ligands directly promote activated CD4+ T cell survival. Journal of Immunology (Baltimore, Md.: 1950), 172, 6065–6073.

    Article  CAS  Google Scholar 

  • Geng, D., Zheng, L., Srivastava, R., Asprodites, N., Velasco-Gonzalez, C., & Davila, E. (2010). When toll-like receptor and T-cell receptor signals collide: A mechanism for enhanced CD8 T-cell effector function. Blood, 116, 3494–3504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gollnick, H., Barona, C. G., Frank, R. G., Ruzicka, T., Megahed, M., Maus, J., & Munzel, U. (2008). Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: Conclusion of a 5-year long-term follow-up study in Europe. European Journal of Dermatology: EJD, 18, 677–682.

    CAS  PubMed  Google Scholar 

  • Gomez, J. A., Wapinski, O. L., Yang, Y. W., Bureau, J. F., Gopinath, S., Monack, D. M., Chang, H. Y., Brahic, M., & Kirkegaard, K. (2013). The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-gamma locus. Cell, 152, 743–754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Reyes, S., Marin, L., Gonzalez, L., Gonzalez, L. O., del Casar, J. M., Lamelas, M. L., Gonzalez-Quintana, J. M., & Vizoso, F. J. (2010). Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC Cancer, 10, 665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grauer, O., Poschl, P., Lohmeier, A., Adema, G. J., & Bogdahn, U. (2007). Toll-like receptor triggered dendritic cell maturation and IL-12 secretion are necessary to overcome T-cell inhibition by glioma-associated TGF-beta2. Journal of Neuro-Oncology, 82, 151–161.

    Article  CAS  PubMed  Google Scholar 

  • Grauer, O. M., Molling, J. W., Bennink, E., Toonen, L. W., Sutmuller, R. P., Nierkens, S., & Adema, G. J. (2008). TLR ligands in the local treatment of established intracerebral murine gliomas. Journal of Immunology, 181, 6720–6729.

    Article  CAS  Google Scholar 

  • Gutschner, T., & Diederichs, S. (2012). The hallmarks of cancer: A long non-coding RNA point of view. RNA Biology, 9, 703–719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., et al. (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 458, 223–227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen, T. B., Kjems, J., & Damgaard, C. K. (2013). Circular RNA and miR-7 in cancer. Cancer Research, 73, 5609–5612.

    Article  CAS  PubMed  Google Scholar 

  • Hartman, L. L., Crawford, J. R., Makale, M. T., Milburn, M., Joshi, S., Salazar, A. M., Hasenauer, B., VandenBerg, S. R., MacDonald, T. J., & Durden, D. L. (2014). Pediatric phase II trials of poly-ICLC in the management of newly diagnosed and recurrent brain tumors. Journal of Pediatric Hematology/Oncology, 36, 451–457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harvey, R. D., & Morgan, E. T. (2014). Cancer, inflammation, and therapy: Effects on cytochrome p450-mediated drug metabolism and implications for novel immunotherapeutic agents. Clinical Pharmacology and Therapeutics, 96, 449–457.

    Article  CAS  PubMed  Google Scholar 

  • Hatziapostolou, M., Polytarchou, C., Aggelidou, E., Drakaki, A., Poultsides, G. A., Jaeger, S. A., Ogata, H., Karin, M., Struhl, K., Hadzopoulou-Cladaras, M., et al. (2011). An HNF4alpha-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell, 147, 1233–1247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hawkins, B. T., & Davis, T. P. (2005). The blood-brain barrier/neurovascular unit in health and disease. Pharmacological Reviews, 57, 173–185.

    Article  CAS  PubMed  Google Scholar 

  • He, M., Xu, Z., Ding, T., Kuang, D. M., & Zheng, L. (2009). MicroRNA-155 regulates inflammatory cytokine production in tumor-associated macrophages via targeting C/EBPbeta. Cellular & Molecular Immunology, 6, 343–352.

    Article  CAS  Google Scholar 

  • He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S., Li, H., Jing, Q., Yan, Y., Zhang, H., et al. (2012). Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment. International Journal of Molecular Medicine, 30, 599–605.

    CAS  PubMed  Google Scholar 

  • Henriques, L., Palumbo, M., Guay, M. P., Bahoric, B., Basik, M., Kavan, P., & Batist, G. (2014). Imiquimod in the treatment of breast cancer skin metastasis. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 32, e22–e25.

    Article  Google Scholar 

  • Hervas-Stubbs, S., Olivier, A., Boisgerault, F., Thieblemont, N., & Leclerc, C. (2007). TLR3 ligand stimulates fully functional memory CD8+ T cells in the absence of CD4+ T-cell help. Blood, 109, 5318–5326.

    Article  CAS  PubMed  Google Scholar 

  • Hesling, C., D’Incan, M., Mansard, S., Franck, F., Corbin-Duval, A., Chevenet, C., Dechelotte, P., Madelmont, J. C., Veyre, A., Souteyrand, P., et al. (2004). In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases. The British Journal of Dermatology, 150, 761–767.

    Article  CAS  PubMed  Google Scholar 

  • Heward, J. A., & Lindsay, M. A. (2014). Long non-coding RNAs in the regulation of the immune response. Trends in Immunology, 35, 408–419.

    Article  CAS  PubMed  Google Scholar 

  • Hodge, L. S., Ziesmer, S. C., Yang, Z. Z., Secreto, F. J., Gertz, M. A., Novak, A. J., & Ansell, S. M. (2012). IL-21 in the bone marrow microenvironment contributes to IgM secretion and proliferation of malignant cells in Waldenstrom macroglobulinemia. Blood, 120, 3774–3782.

    Article  CAS  PubMed  Google Scholar 

  • Holmstrom, K., Pedersen, A. W., Claesson, M. H., Zocca, M. B., & Jensen, S. S. (2010). Identification of a microRNA signature in dendritic cell vaccines for cancer immunotherapy. Human Immunology, 71, 67–73.

    Article  CAS  PubMed  Google Scholar 

  • Hua, D., Liu, M. Y., Cheng, Z. D., Qin, X. J., Zhang, H. M., Chen, Y., Qin, G. J., Liang, G., Li, J. N., Han, X. F., et al. (2009). Small interfering RNA-directed targeting of Toll-like receptor 4 inhibits human prostate cancer cell invasion, survival, and tumorigenicity. Molecular Immunology, 46, 2876–2884.

    Article  CAS  PubMed  Google Scholar 

  • Huang, B., Zhao, J., Li, H., He, K. L., Chen, Y., Chen, S. H., Mayer, L., Unkeless, J. C., & Xiong, H. (2005). Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Research, 65, 5009–5014.

    Article  CAS  PubMed  Google Scholar 

  • Huang, B., Zhao, J., Shen, S., Li, H., He, K. L., Shen, G. X., Mayer, L., Unkeless, J., Li, D., Yuan, Y., et al. (2007). Listeria monocytogenes promotes tumor growth via tumor cell toll-like receptor 2 signaling. Cancer Research, 67, 4346–4352.

    Article  CAS  PubMed  Google Scholar 

  • Huang, E., Liu, R., & Chu, Y. (2015). miRNA-15a/16: As tumor suppressors and more. Future Oncology, 11, 2351–2363.

    Article  CAS  PubMed  Google Scholar 

  • Huarte, M., & Rinn, J. L. (2010). Large non-coding RNAs: Missing links in cancer? Human Molecular Genetics, 19, R152–R161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huffaker, T. B., Hu, R., Runtsch, M. C., Bake, E., Chen, X., Zhao, J., Round, J. L., Baltimore, D., & O’Connell, R. M. (2012). Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity. Cell Reports, 2, 1697–1709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang do, W., Son, S., Jang, J., Youn, H., Lee, S., Lee, D., Lee, Y. S., Jeong, J. M., Kim, W. J., & Lee, D. S. (2011). A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA. Biomaterials, 32, 4968–4975.

    Article  PubMed  CAS  Google Scholar 

  • Ifere, G. O., & Ananaba, G. A. (2009). Prostate cancer gene expression marker 1 (PCGEM1): A patented prostate- specific non-coding gene and regulator of prostate cancer progression. Recent Patents on DNA & Gene Sequences, 3, 151–163.

    Article  CAS  Google Scholar 

  • Iliopoulos, D., Jaeger, S. A., Hirsch, H. A., Bulyk, M. L., & Struhl, K. (2010). STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Molecular Cell, 39, 493–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ilvesaro, J. M., Merrell, M. A., Swain, T. M., Davidson, J., Zayzafoon, M., Harris, K. W., & Selander, K. S. (2007). Toll like receptor-9 agonists stimulate prostate cancer invasion in vitro. The Prostate, 67, 774–781.

    Article  CAS  PubMed  Google Scholar 

  • Janssen, H. L., Reesink, H. W., Lawitz, E. J., Zeuzem, S., Rodriguez-Torres, M., Patel, K., van der Meer, A. J., Patick, A. K., Chen, A., Zhou, Y., et al. (2013). Treatment of HCV infection by targeting microRNA. The New England Journal of Medicine, 368, 1685–1694.

    Article  CAS  PubMed  Google Scholar 

  • Jego, G., Bataille, R., Geffroy-Luseau, A., Descamps, G., & Pellat-Deceunynck, C. (2006). Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors. Leukemia, 20, 1130–1137.

    Article  CAS  PubMed  Google Scholar 

  • Jelinek, I., Leonard, J. N., Price, G. E., Brown, K. N., Meyer-Manlapat, A., Goldsmith, P. K., Wang, Y., Venzon, D., Epstein, S. L., & Segal, D. M. (2011). TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. Journal of Immunology, 186, 2422–2429.

    Article  CAS  Google Scholar 

  • Jewett, A., & Bonavida, B. (1995). Interferon-alpha activates cytotoxic function but inhibits interleukin-2-mediated proliferation and tumor necrosis factor-alpha secretion by immature human natural killer cells. Journal of Clinical Immunology, 15, 35–44.

    Article  CAS  PubMed  Google Scholar 

  • Ji, X., Li, J., Xu, L., Wang, W., Luo, M., Luo, S., Ma, L., Li, K., Gong, S., He, L., et al. (2013). IL4 and IL-17A provide a Th2/Th17-polarized inflammatory milieu in favor of TGF-beta1 to induce bronchial epithelial-mesenchymal transition (EMT). International Journal of Clinical and Experimental Pathology, 6, 1481–1492.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang, P., Liu, R., Zheng, Y., Liu, X., Chang, L., Xiong, S., & Chu, Y. (2012). MiR-34a inhibits lipopolysaccharide-induced inflammatory response through targeting Notch1 in murine macrophages. Experimental Cell Research, 318, 1175–1184.

    Article  CAS  PubMed  Google Scholar 

  • Jin, M. S., & Lee, J. O. (2008). Structures of the toll-like receptor family and its ligand complexes. Immunity, 29, 182–191.

    Article  CAS  PubMed  Google Scholar 

  • Kabelitz, D. (2007). Expression and function of Toll-like receptors in T lymphocytes. Current Opinion in Immunology, 19, 39–45.

    Article  CAS  PubMed  Google Scholar 

  • Kang, J. Y., & Lee, J. O. (2011). Structural biology of the Toll-like receptor family. Annual Review of Biochemistry, 80, 917–941.

    Article  CAS  PubMed  Google Scholar 

  • Kawagoe, T., Sato, S., Matsushita, K., Kato, H., Matsui, K., Kumagai, Y., Saitoh, T., Kawai, T., Takeuchi, O., & Akira, S. (2008). Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2. Nature Immunology, 9, 684–691.

    Article  CAS  PubMed  Google Scholar 

  • Kawai, T., & Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: Update on toll-like receptors. Nature Immunology, 11, 373–384.

    Article  CAS  PubMed  Google Scholar 

  • Kawai, T., & Akira, S. (2011). Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity, 34, 637–650.

    Article  CAS  PubMed  Google Scholar 

  • Kelly, M. G., Alvero, A. B., Chen, R., Silasi, D. A., Abrahams, V. M., Chan, S., Visintin, I., Rutherford, T., & Mor, G. (2006). TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Research, 66, 3859–3868.

    Article  CAS  PubMed  Google Scholar 

  • Killeen, S. D., Wang, J. H., Andrews, E. J., & Redmond, H. P. (2009). Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system. British Journal of Cancer, 100, 1589–1602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, T.-H., Jiang, H.-L., Jere, D., Park, I.-K., Cho, M.-H., Nah, J.-W., Choi, Y.-J., Akaike, T., & Cho, C.-S. (2007). Chemical modification of chitosan as a gene carrier in vitro and in vivo. Progress in Polymer Science, 32, 726–753.

    Article  CAS  Google Scholar 

  • Kim, Y. H., Girardi, M., Duvic, M., Kuzel, T., Link, B. K., Pinter-Brown, L., & Rook, A. H. (2010). Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma. Journal of the American Academy of Dermatology, 63, 975–983.

    Article  CAS  PubMed  Google Scholar 

  • Kim, J. S., Yu, S. K., Lee, M. H., Park, M. G., Park, E., Kim, S. G., Lee, S. Y., Kim, C. S., Kim, H. J., Chun, H. S., et al. (2013). MicroRNA-205 directly regulates the tumor suppressor, interleukin-24, in human KB oral cancer cells. Molecules and Cells, 35, 17–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirigin, F. F., Lindstedt, K., Sellars, M., Ciofani, M., Low, S. L., Jones, L., Bell, F., Pauli, F., Bonneau, R., Myers, R. M., et al. (2012). Dynamic microRNA gene transcription and processing during T cell development. Journal of Immunology (Baltimore, Md.: 1950), 188, 3257–3267.

    Article  CAS  Google Scholar 

  • Koukos, G., Polytarchou, C., Kaplan, J. L., Morley-Fletcher, A., Gras-Miralles, B., Kokkotou, E., Baril-Dore, M., Pothoulakis, C., Winter, H. S., & Iliopoulos, D. (2013). MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology, 145, 842–852.e842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krawczyk, M., & Emerson, B. M. (2014). p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-kappaB complexes. eLife, 3, e01776.

    Article  PubMed  PubMed Central  Google Scholar 

  • Krishnamurthy, S., Warner, K. A., Dong, Z., Imai, A., Nor, C., Ward, B. B., Helman, J. I., Taichman, R. S., Bellile, E. L., McCauley, L. K., et al. (2014). Endothelial interleukin-6 defines the tumorigenic potential of primary human cancer stem cells. Stem Cells, 32, 2845–2857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krummen, M., Balkow, S., Shen, L., Heinz, S., Loquai, C., Probst, H. C., & Grabbe, S. (2010). Release of IL-12 by dendritic cells activated by TLR ligation is dependent on MyD88 signaling, whereas TRIF signaling is indispensable for TLR synergy. Journal of Leukocyte Biology, 88, 189–199.

    Article  CAS  PubMed  Google Scholar 

  • Kryczek, I., Lin, Y., Nagarsheth, N., Peng, D., Zhao, L., Zhao, E., Vatan, L., Szeliga, W., Dou, Y., Owens, S., et al. (2014). IL-22(+)CD4(+) T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity, 40, 772–784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kundu, S. D., Lee, C., Billips, B. K., Habermacher, G. M., Zhang, Q., Liu, V., Wong, L. Y., Klumpp, D. J., & Thumbikat, P. (2008). The toll-like receptor pathway: A novel mechanism of infection-induced carcinogenesis of prostate epithelial cells. The Prostate, 68, 223–229.

    Article  CAS  PubMed  Google Scholar 

  • Kuroki, M., Miyamoto, S., Morisaki, T., Yotsumoto, F., Shirasu, N., Taniguchi, Y., & Soma, G. (2012). Biological response modifiers used in cancer biotherapy. Anticancer Research, 32, 2229–2233.

    CAS  PubMed  Google Scholar 

  • Kurreck, J., Wyszko, E., Gillen, C., & Erdmann, V. A. (2002). Design of antisense oligonucleotides stabilized by locked nucleic acids. Nucleic Acids Research, 30, 1911–1918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kwissa, M., Nakaya, H. I., Oluoch, H., & Pulendran, B. (2012). Distinct TLR adjuvants differentially stimulate systemic and local innate immune responses in nonhuman primates. Blood, 119, 2044–2055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lampron, A., Elali, A., & Rivest, S. (2013). Innate immunity in the CNS: Redefining the relationship between the CNS and its environment. Neuron, 78, 214–232.

    Article  CAS  PubMed  Google Scholar 

  • Lasek, W., Zagozdzon, R., & Jakobisiak, M. (2014). Interleukin 12: Still a promising candidate for tumor immunotherapy? Cancer Immunology, Immunotherapy: CII, 63, 419–435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, Y. S., & Dutta, A. (2009). MicroRNAs in cancer. Annual Review of Pathology, 4, 199–227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, S., & Margolin, K. (2011). Cytokines in cancer immunotherapy. Cancers, 3, 3856–3893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lerner, M., Harada, M., Loven, J., Castro, J., Davis, Z., Oscier, D., Henriksson, M., Sangfelt, O., Grander, D., & Corcoran, M. M. (2009). DLEU2, frequently deleted in malignancy, functions as a critical host gene of the cell cycle inhibitory microRNAs miR-15a and miR-16-1. Experimental Cell Research, 315, 2941–2952.

    Article  CAS  PubMed  Google Scholar 

  • Li, Y. P., Gottwein, J. M., Scheel, T. K., Jensen, T. B., & Bukh, J. (2011). MicroRNA-122 antagonism against hepatitis C virus genotypes 1-6 and reduced efficacy by host RNA insertion or mutations in the HCV 5′ UTR. Proceedings of the National Academy of Sciences of the United States of America, 108, 4991–4996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, J., Mo, H. Y., Xiong, G., Zhang, L., He, J., Huang, Z. F., Liu, Z. W., Chen, Q. Y., Du, Z. M., Zheng, L. M., et al. (2012a). Tumor microenvironment macrophage inhibitory factor directs the accumulation of interleukin-17-producing tumor-infiltrating lymphocytes and predicts favorable survival in nasopharyngeal carcinoma patients. Journal of Biological Chemistry, 287, 35484–35495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, Y., Wang, L., Pappan, L., Galliher-Beckley, A., & Shi, J. (2012b). IL-1beta promotes stemness and invasiveness of colon cancer cells through Zeb1 activation. Molecular Cancer, 11, 87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li, L., Zhang, J., Diao, W., Wang, D., Wei, Y., Zhang, C. Y., & Zen, K. (2014a). MicroRNA-155 and MicroRNA-21 promote the expansion of functional myeloid-derived suppressor cells. Journal of Immunology (Baltimore, Md.: 1950), 192, 1034–1043.

    Article  CAS  Google Scholar 

  • Li, Z., Chao, T. C., Chang, K. Y., Lin, N., Patil, V. S., Shimizu, C., Head, S. R., Burns, J. C., & Rana, T. M. (2014b). The long noncoding RNA THRIL regulates TNFalpha expression through its interaction with hnRNPL. Proceedings of the National Academy of Sciences of the United States of America, 111, 1002–1007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang, X., De Vera, M. E., Buchser, W. J., Romo de Vivar Chavez, A., Loughran, P., Beer Stolz, D., Basse, P., Wang, T., Van Houten, B., Zeh, H. J., 3rd, et al. (2012). Inhibiting systemic autophagy during interleukin 2 immunotherapy promotes long-term tumor regression. Cancer Research, 72, 2791–2801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin, R., Chen, L., Chen, G., Hu, C., Jiang, S., Sevilla, J., Wan, Y., Sampson, J. H., Zhu, B., & Li, Q. J. (2014). Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression. Journal of Clinical Investigation, 124, 5352–5367.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lindsay, M. A. (2008). microRNAs and the immune response. Trends in Immunology, 29, 343–351.

    Article  CAS  PubMed  Google Scholar 

  • Liu, H., Komai-Koma, M., Xu, D., & Liew, F. Y. (2006). Toll-like receptor 2 signaling modulates the functions of CD4+ CD25+ regulatory T cells. Proceedings of the National Academy of Sciences of the United States of America, 103, 7048–7053.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, Y., Lai, L., Chen, Q., Song, Y., Xu, S., Ma, F., Wang, X., Wang, J., Yu, H., Cao, X., et al. (2012). MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. Journal of Immunology (Baltimore, Md.: 1950), 188, 5500–5510.

    Article  CAS  Google Scholar 

  • Liu, R., Gu, J., Jiang, P., Zheng, Y., Liu, X., Jiang, X., Huang, E., Xiong, S., Xu, F., Liu, G., et al. (2015). DNMT1-microRNA126 epigenetic circuit contributes to esophageal squamous cell carcinoma growth via ADAM9-EGFR-AKT signaling. Clinical Cancer Research: Official Journal of the American Association for Cancer Research, 21, 854–863.

    Article  CAS  Google Scholar 

  • Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., et al. (2015). Structural and functional features of central nervous system lymphatic vessels. Nature, 523, 337–341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lowther, D. E., & Hafler, D. A. (2012). Regulatory T cells in the central nervous system. Immunological Reviews, 248, 156–169.

    Article  PubMed  Google Scholar 

  • Lu, H., Yang, Y., Gad, E., Wenner, C. A., Chang, A., Larson, E. R., Dang, Y., Martzen, M., Standish, L. J., & Disis, M. L. (2011). Polysaccharide krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells. Clinical Cancer Research: Official Journal of the American Association for Cancer Research, 17, 67–76.

    Article  CAS  Google Scholar 

  • Luo, J. L., Maeda, S., Hsu, L. C., Yagita, H., & Karin, M. (2004). Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. Cancer Cell, 6, 297–305.

    Article  CAS  PubMed  Google Scholar 

  • Lv, H., Zhang, S., Wang, B., Cui, S., & Yan, J. (2006). Toxicity of cationic lipids and cationic polymers in gene delivery. Journal of Controlled Release: Official Journal of the Controlled Release Society, 114, 100–109.

    Article  CAS  Google Scholar 

  • Maiorano, N. A., & Mallamaci, A. (2009). Promotion of embryonic cortico-cerebral neuronogenesis by miR-124. Neural Development, 4, 40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Majid, S., Dar, A. A., Saini, S., Yamamura, S., Hirata, H., Tanaka, Y., Deng, G., & Dahiya, R. (2010). MicroRNA-205-directed transcriptional activation of tumor suppressor genes in prostate cancer. Cancer, 116, 5637–5649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manegold, C., van Zandwijk, N., Szczesna, A., Zatloukal, P., Au, J. S., Blasinska-Morawiec, M., Serwatowski, P., Krzakowski, M., Jassem, J., Tan, E. H., et al. (2012). A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer. Annals of Oncology: Official Journal European Society Medical Oncology/ESMO, 23, 72–77.

    Article  CAS  Google Scholar 

  • Mantovani, A., & Locati, M. (2013). Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: Lessons and open questions. Arteriosclerosis, Thrombosis, and Vascular Biology, 33, 1478–1483.

    Article  CAS  PubMed  Google Scholar 

  • Marshall, N. A., Galvin, K. C., Corcoran, A. M., Boon, L., Higgs, R., & Mills, K. H. (2012). Immunotherapy with PI3K inhibitor and Toll-like receptor agonist induces IFN-gamma+IL-17+ polyfunctional T cells that mediate rejection of murine tumors. Cancer Research, 72, 581–591.

    Article  CAS  PubMed  Google Scholar 

  • McCarron, M., & Reen, D. J. (2009). Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation. Journal of Immunology (Baltimore, Md.: 1950), 182, 55–62.

    Article  CAS  Google Scholar 

  • Medzhitov, R., Preston-Hurlburt, P., Kopp, E., Stadlen, A., Chen, C., Ghosh, S., & Janeway, C. A., Jr. (1998). MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Molecular Cell, 2, 253–258.

    Article  CAS  PubMed  Google Scholar 

  • Mellor, A. L., Baban, B., Chandler, P. R., Manlapat, A., Kahler, D. J., & Munn, D. H. (2005). Cutting edge: CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase-dependent T cell regulatory functions via IFN Type 1 signaling. Journal of Immunology (Baltimore, Md.: 1950), 175, 5601–5605.

    Article  CAS  Google Scholar 

  • Metzler, M., Wilda, M., Busch, K., Viehmann, S., & Borkhardt, A. (2004). High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes, Chromosomes & Cancer, 39, 167–169.

    Article  CAS  Google Scholar 

  • Meyer, T., Surber, C., French, L. E., & Stockfleth, E. (2013). Resiquimod, a topical drug for viral skin lesions and skin cancer. Expert Opinion on Investigational Drugs, 22, 149–159.

    Article  CAS  PubMed  Google Scholar 

  • Miao, J. W., Liu, L. J., & Huang, J. (2014). Interleukin-6-induced epithelial-mesenchymal transition through signal transducer and activator of transcription 3 in human cervical carcinoma. International Journal of Oncology, 45, 165–176.

    CAS  PubMed  Google Scholar 

  • Micali, G., Lacarrubba, F., Nasca, M. R., Ferraro, S., & Schwartz, R. A. (2014). Topical pharmacotherapy for skin cancer: Part II. Clinical applications. Journal of the American Academy of Dermatology, 70, 979. e971-912; quiz 9912; quiz 9912.

    Article  PubMed  CAS  Google Scholar 

  • Miller, R. P., Tadagavadi, R. K., Ramesh, G., & Reeves, W. B. (2010). Mechanisms of cisplatin nephrotoxicity. Toxins, 2, 2490–2518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Min, S., Liang, X., Zhang, M., Zhang, Y., Mei, S., Liu, J., Liu, J., Su, X., Cao, S., Zhong, X., et al. (2013). Multiple tumor-associated microRNAs modulate the survival and longevity of dendritic cells by targeting YWHAZ and Bcl2 signaling pathways. Journal of Immunology, 190, 2437–2446.

    Article  CAS  Google Scholar 

  • Misso, G., Di Martino, M. T., De Rosa, G., Farooqi, A. A., Lombardi, A., Campani, V., Zarone, M. R., Gulla, A., Tagliaferri, P., Tassone, P., et al. (2014). Mir-34: A new weapon against cancer? Molecular Therapy Nucleic Acids, 3, e194.

    Article  CAS  PubMed  Google Scholar 

  • Muthuswamy, R., Wang, L., Pitteroff, J., Gingrich, J. R., & Kalinski, P. (2015). Combination of IFNalpha and poly-I:C reprograms bladder cancer microenvironment for enhanced CTL attraction. Journal for Immunotherapy of Cancer, 3, 6.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ngiow, S. F., Teng, M. W., & Smyth, M. J. (2013). A balance of interleukin-12 and -23 in cancer. Trends in Immunology, 34, 548–555.

    Article  CAS  PubMed  Google Scholar 

  • Nierkens, S., den Brok, M. H., Garcia, Z., Togher, S., Wagenaars, J., Wassink, M., Boon, L., Ruers, T. J., Figdor, C. G., Schoenberger, S. P., et al. (2011). Immune adjuvant efficacy of CpG oligonucleotide in cancer treatment is founded specifically upon TLR9 function in plasmacytoid dendritic cells. Cancer Research, 71, 6428–6437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Northfelt, D. W., Ramanathan, R. K., Cohen, P. A., Von Hoff, D. D., Weiss, G. J., Dietsch, G. N., Manjarrez, K. L., Randall, T. D., & Hershberg, R. M. (2014). A phase I dose-finding study of the novel toll-like receptor 8 agonist VTX-2337 in adult subjects with advanced solid tumors or lymphoma. Clinical Cancer Research: Official Journal of the American Association for Cancer Research, 20, 3683–3691.

    Article  CAS  Google Scholar 

  • Okada, H., Kohanbash, G., & Lotze, M. T. (2010). MicroRNAs in immune regulation – opportunities for cancer immunotherapy. International Journal of Biochemistry & Cell Biology, 42, 1256–1261.

    Article  CAS  Google Scholar 

  • Olson, J. K., & Miller, S. D. (2004). Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. Journal of Immunology, 173, 3916–3924.

    Article  CAS  Google Scholar 

  • Ousman, S. S., & Kubes, P. (2012). Immune surveillance in the central nervous system. Nature Neuroscience, 15, 1096–1101.

    Article  CAS  PubMed  Google Scholar 

  • Pagani, M., Rossetti, G., Panzeri, I., de Candia, P., Bonnal, R. J., Rossi, R. L., Geginat, J., & Abrignani, S. (2013). Role of microRNAs and long-non-coding RNAs in CD4(+) T-cell differentiation. Immunological Reviews, 253, 82–96.

    Article  PubMed  CAS  Google Scholar 

  • Palma, G., Barbieri, A., Bimonte, S., Palla, M., Zappavigna, S., Caraglia, M., Ascierto, P. A., Ciliberto, G., & Arra, C. (2013). Interleukin 18: Friend or foe in cancer. Biochimica et Biophysica Acta, 1836, 296–303.

    CAS  PubMed  Google Scholar 

  • Pang, K. C., Dinger, M. E., Mercer, T. R., Malquori, L., Grimmond, S. M., Chen, W., & Mattick, J. S. (2009). Genome-wide identification of long noncoding RNAs in CD8+ T cells. Journal of Immunology (Baltimore, Md.: 1950), 182, 7738–7748.

    Article  CAS  Google Scholar 

  • Park, S. J., Cheon, E. J., Lee, M. H., & Kim, H. A. (2013). MicroRNA-127-5p regulates matrix metalloproteinase 13 expression and interleukin-1beta-induced catabolic effects in human chondrocytes. Arthritis and Rheumatism, 65, 3141–3152.

    Article  CAS  PubMed  Google Scholar 

  • Pashenkov, M., Goess, G., Wagner, C., Hormann, M., Jandl, T., Moser, A., Britten, C. M., Smolle, J., Koller, S., Mauch, C., et al. (2006). Phase II trial of a toll-like receptor 9-activating oligonucleotide in patients with metastatic melanoma. Journal of Controlled Release: Official Journal of the Controlled Release Society, 24, 5716–5724.

    CAS  Google Scholar 

  • Patel, S. A., Bhambra, U., Charalambous, M. P., David, R. M., Edwards, R. J., Lightfoot, T., Boobis, A. R., & Gooderham, N. J. (2014). Interleukin-6 mediated upregulation of CYP1B1 and CYP2E1 in colorectal cancer involves DNA methylation, miR27b and STAT3. British Journal of Cancer, 111, 2287–2296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng, G., Guo, Z., Kiniwa, Y., Voo, K. S., Peng, W., Fu, T., Wang, D. Y., Li, Y., Wang, H. Y., & Wang, R. F. (2005). Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science (New York, NY), 309, 1380–1384.

    Article  CAS  Google Scholar 

  • Peschansky, V. J., & Wahlestedt, C. (2014). Non-coding RNAs as direct and indirect modulators of epigenetic regulation. Epigenetics: Official Journal of the DNA Methylation Society, 9, 3–12.

    Article  CAS  Google Scholar 

  • Peters, U., Jiao, S., Schumacher, F. R., Hutter, C. M., Aragaki, A. K., Baron, J. A., Berndt, S. I., Bezieau, S., Brenner, H., Butterbach, K., et al. (2013). Identification of genetic susceptibility loci for colorectal tumors in a genome-wide meta-analysis. Gastroenterology, 144, 799–807.e724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petrella, T., Quirt, I., Verma, S., Haynes, A. E., Charette, M., Bak, K., & Melanoma Disease Site Group of Cancer Care Ontario’s Program in Evidence-based, C. (2007). Single-agent interleukin-2 in the treatment of metastatic melanoma: A systematic review. Cancer Treatment Reviews, 33, 484–496.

    Article  CAS  PubMed  Google Scholar 

  • Pille, J. Y., Li, H., Blot, E., Bertrand, J. R., Pritchard, L. L., Opolon, P., Maksimenko, A., Lu, H., Vannier, J. P., Soria, J., et al. (2006). Intravenous delivery of anti-RhoA small interfering RNA loaded in nanoparticles of chitosan in mice: Safety and efficacy in xenografted aggressive breast cancer. Human Gene Therapy, 17, 1019–1026.

    Article  CAS  PubMed  Google Scholar 

  • Ponting, C. P., Oliver, P. L., & Reik, W. (2009). Evolution and functions of long noncoding RNAs. Cell, 136, 629–641.

    Article  CAS  PubMed  Google Scholar 

  • Preusser, M., de Ribaupierre, S., Wohrer, A., Erridge, S. C., Hegi, M., Weller, M., & Stupp, R. (2011). Current concepts and management of glioblastoma. Annals of Neurology, 70, 9–21.

    Article  PubMed  Google Scholar 

  • Prins, R. M., Craft, N., Bruhn, K. W., Khan-Farooqi, H., Koya, R. C., Stripecke, R., Miller, J. F., & Liau, L. M. (2006). The TLR-7 agonist, imiquimod, enhances dendritic cell survival and promotes tumor antigen-specific T cell priming: Relation to central nervous system antitumor immunity. Journal of Immunology, 176, 157–164.

    Article  CAS  Google Scholar 

  • Prins, R. M., Soto, H., Konkankit, V., Odesa, S. K., Eskin, A., Yong, W. H., Nelson, S. F., & Liau, L. M. (2011). Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clinical Cancer Research: Official Journal of the American Association for Cancer Research, 17, 1603–1615.

    Article  CAS  Google Scholar 

  • Pucci, F., & Pittet, M. J. (2013). Molecular pathways: Tumor-derived microvesicles and their interactions with immune cells in vivo. Clinical Cancer Research, 19, 2598–2604.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Qian, B. Z., & Pollard, J. W. (2010). Macrophage diversity enhances tumor progression and metastasis. Cell, 141, 39–51.

    Article  CAS  PubMed  Google Scholar 

  • Qian, X., Gu, L., Ning, H., Zhang, Y., Hsueh, E. C., Fu, M., Hu, X., Wei, L., Hoft, D. F., & Liu, J. (2013). Increased Th17 cells in the tumor microenvironment is mediated by IL-23 via tumor-secreted prostaglandin E2. Journal of Immunology, 190, 5894–5902.

    Article  CAS  Google Scholar 

  • Rahman, A. H., Taylor, D. K., & Turka, L. A. (2009). The contribution of direct TLR signaling to T cell responses. Immunologic Research, 45, 25–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raisch, J., Darfeuille-Michaud, A., & Nguyen, H. T. (2013). Role of microRNAs in the immune system, inflammation and cancer. World Journal of Gastroenterology, 19, 2985–2996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ravindran, C., Cheng, Y. C., & Liang, S. M. (2010). CpG-ODNs induces up-regulated expression of chemokine CCL9 in mouse macrophages and microglia. Cellular Immunology, 260, 113–118.

    Article  CAS  PubMed  Google Scholar 

  • Ren, Y., Kang, C. S., Yuan, X. B., Zhou, X., Xu, P., Han, L., Wang, G. X., Jia, Z., Zhong, Y., Yu, S., et al. (2010a). Co-delivery of as-miR-21 and 5-FU by poly(amidoamine) dendrimer attenuates human glioma cell growth in vitro. Journal of Biomaterials Science Polymer Edition, 21, 303–314.

    Article  CAS  PubMed  Google Scholar 

  • Ren, Y., Zhou, X., Mei, M., Yuan, X. B., Han, L., Wang, G. X., Jia, Z. F., Xu, P., Pu, P. Y., & Kang, C. S. (2010b). MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol. BMC Cancer, 10, 27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rhee, S. H., Im, E., & Pothoulakis, C. (2008). Toll-like receptor 5 engagement modulates tumor development and growth in a mouse xenograft model of human colon cancer. Gastroenterology, 135, 518–528.

    Article  CAS  PubMed  Google Scholar 

  • Ridgway, D. (2003). The first 1000 dendritic cell vaccinees. Cancer Investigation, 21, 873–886.

    Article  PubMed  Google Scholar 

  • Robertson, M. J., Kline, J., Struemper, H., Koch, K. M., Bauman, J. W., Gardner, O. S., Murray, S. C., Germaschewski, F., Weisenbach, J., Jonak, Z., et al. (2013). A dose-escalation study of recombinant human interleukin-18 in combination with rituximab in patients with non-Hodgkin lymphoma. Journal of Immunotherapy (Hagerstown, Md: 1997), 36, 331–341.

    CAS  Google Scholar 

  • Rosenfeld, M. R., Chamberlain, M. C., Grossman, S. A., Peereboom, D. M., Lesser, G. J., Batchelor, T. T., Desideri, S., Salazar, A. M., & Ye, X. (2010). A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma. Neuro-Oncology, 12, 1071–1077.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruckerl, D., Jenkins, S. J., Laqtom, N. N., Gallagher, I. J., Sutherland, T. E., Duncan, S., Buck, A. H., & Allen, J. E. (2012). Induction of IL-4Ralpha-dependent microRNAs identifies PI3K/Akt signaling as essential for IL-4-driven murine macrophage proliferation in vivo. Blood, 120, 2307–2316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rydberg, C., Mansson, A., Uddman, R., Riesbeck, K., & Cardell, L. O. (2009). Toll-like receptor agonists induce inflammation and cell death in a model of head and neck squamous cell carcinomas. Immunology, 128, e600–e611.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sabado, R. L., Pavlick, A., Gnjatic, S., Cruz, C. M., Vengco, I., Hasan, F., Spadaccia, M., Darvishian, F., Chiriboga, L., Holman, R. M., et al. (2015). Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma. Cancer Immunology Research, 3, 278–287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sabbatini, P., Tsuji, T., Ferran, L., Ritter, E., Sedrak, C., Tuballes, K., Jungbluth, A. A., Ritter, G., Aghajanian, C., Bell-McGuinn, K., et al. (2012). Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clinical Cancer Research: Official Journal of the American Association for Cancer Research, 18, 6497–6508.

    Article  CAS  Google Scholar 

  • Sahoo, A., & Im, S. H. (2010). Interleukin and interleukin receptor diversity: Role of alternative splicing. International Reviews of Immunology, 29, 77–109.

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi, S. (2000). Regulatory T cells: Key controllers of immunologic self-tolerance. Cell, 101, 455–458.

    Article  CAS  PubMed  Google Scholar 

  • Salaun, B., Coste, I., Rissoan, M. C., Lebecque, S. J., & Renno, T. (2006). TLR3 can directly trigger apoptosis in human cancer cells. Journal of Immunology (Baltimore, Md.: 1950), 176, 4894–4901.

    Article  CAS  Google Scholar 

  • Saraiva, M., & O’Garra, A. (2010). The regulation of IL-10 production by immune cells. Nature Reviews Immunology, 10, 170–181.

    Article  CAS  PubMed  Google Scholar 

  • Sauder, D. N., Smith, M. H., Senta-McMillian, T., Soria, I., & Meng, T. C. (2003). Randomized, single-blind, placebo-controlled study of topical application of the immune response modulator resiquimod in healthy adults. Antimicrobial Agents and Chemotherapy, 47, 3846–3852.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheel, B., Aulwurm, S., Probst, J., Stitz, L., Hoerr, I., Rammensee, H. G., Weller, M., & Pascolo, S. (2006). Therapeutic anti-tumor immunity triggered by injections of immunostimulating single-stranded RNA. European Journal of Immunology, 36, 2807–2816.

    Article  CAS  PubMed  Google Scholar 

  • Schmoll, H. J., Wittig, B., Arnold, D., Riera-Knorrenschild, J., Nitsche, D., Kroening, H., Mayer, F., Andel, J., Ziebermayr, R., & Scheithauer, W. (2014). Maintenance treatment with the immunomodulator MGN1703, a toll-like receptor 9 (TLR9) agonist, in patients with metastatic colorectal carcinoma and disease control after chemotherapy: A randomised, double-blind, placebo-controlled trial. Journal of Cancer Research and Clinical Oncology, 140, 1615–1624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulze, H. J., Cribier, B., Requena, L., Reifenberger, J., Ferrandiz, C., Garcia Diez, A., Tebbs, V., & McRae, S. (2005). Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: Results from a randomized vehicle-controlled phase III study in Europe. The British Journal of Dermatology, 152, 939–947.

    Article  CAS  PubMed  Google Scholar 

  • Scomparin, A., Polyak, D., Krivitsky, A., & Satchi-Fainaro, R. (2015). Achieving successful delivery of oligonucleotides – From physico-chemical characterization to in vivo evaluation. Biotechnology Advances, 33, 1294–1309.

    Article  CAS  PubMed  Google Scholar 

  • Seif, A. E., Barrett, D. M., Milone, M., Brown, V. I., Grupp, S. A., & Reid, G. S. (2009). Long-term protection from syngeneic acute lymphoblastic leukemia by CpG ODN-mediated stimulation of innate and adaptive immune responses. Blood, 114, 2459–2466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seki, E., Tsutsui, H., Tsuji, N. M., Hayashi, N., Adachi, K., Nakano, H., Futatsugi-Yumikura, S., Takeuchi, O., Hoshino, K., Akira, S., et al. (2002). Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice. Journal of Immunology (Baltimore, Md.: 1950), 169, 3863–3868.

    Article  CAS  Google Scholar 

  • Serafini, P., Borrello, I., & Bronte, V. (2006). Myeloid suppressor cells in cancer: Recruitment, phenotype, properties, and mechanisms of immune suppression. Seminars in Cancer Biology, 16, 53–65.

    Article  CAS  PubMed  Google Scholar 

  • Shalapour, S., Font-Burgada, J., Di Caro, G., Zhong, Z., Sanchez-Lopez, E., Dhar, D., Willimsky, G., Ammirante, M., Strasner, A., Hansel, D. E., et al. (2015). Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy. Nature, 521, 94–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma, S., Findlay, G. M., Bandukwala, H. S., Oberdoerffer, S., Baust, B., Li, Z., Schmidt, V., Hogan, P. G., Sacks, D. B., & Rao, A. (2011). Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proceedings of the National Academy of Sciences of the United States of America, 108, 11381–11386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheedy, F. J., Palsson-McDermott, E., Hennessy, E. J., Martin, C., O’Leary, J. J., Ruan, Q., Johnson, D. S., Chen, Y., & O’Neill, L. A. (2010). Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nature Immunology, 11, 141–147.

    Article  CAS  PubMed  Google Scholar 

  • Shen, H., Tesar, B. M., Walker, W. E., & Goldstein, D. R. (2008). Dual signaling of MyD88 and TRIF is critical for maximal TLR4-induced dendritic cell maturation. Journal of Immunology, 181, 1849–1858.

    Article  CAS  Google Scholar 

  • Shi, M., Yao, Y., Han, F., Li, Y., & Li, Y. (2014). MAP1S controls breast cancer cell TLR5 signaling pathway and promotes TLR5 signaling-based tumor suppression. PloS One, 9, e86839.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shimizu, T., Yokota, S., Takahashi, S., Kunishima, Y., Takeyama, K., Masumori, N., Takahashi, A., Matsukawa, M., Itoh, N., Tsukamoto, T., et al. (2004). Membrane-anchored CD14 is important for induction of interleukin-8 by lipopolysaccharide and peptidoglycan in uroepithelial cells. Clinical and Diagnostic Laboratory Immunology, 11, 969–976.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sica, A., & Bronte, V. (2007). Altered macrophage differentiation and immune dysfunction in tumor development. Journal of Clinical Investigation, 117, 1155–1166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegal, F. P., Kadowaki, N., Shodell, M., Fitzgerald-Bocarsly, P. A., Shah, K., Ho, S., Antonenko, S., & Liu, Y. J. (1999). The nature of the principal type 1 interferon-producing cells in human blood. Science (New York, NY), 284, 1835–1837.

    Article  CAS  Google Scholar 

  • Sim, G. C., & Radvanyi, L. (2014). The IL-2 cytokine family in cancer immunotherapy. Cytokine & Growth Factor Reviews, 25, 377–390.

    Article  CAS  Google Scholar 

  • Slaby, O., Svoboda, M., Fabian, P., Smerdova, T., Knoflickova, D., Bednarikova, M., Nenutil, R., & Vyzula, R. (2007). Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology, 72, 397–402.

    Article  CAS  PubMed  Google Scholar 

  • Smit, E., Oberholzer, H. M., & Pretorius, E. (2009). A review of immunomodulators with reference to Canova. Homeopathy, 98, 169–176.

    Article  CAS  PubMed  Google Scholar 

  • Smith, E. B., Schwartz, M., Kawamoto, H., You, X., Hwang, D., Liu, H., & Scherr, D. S. (2007). Antitumor effects of imidazoquinolines in urothelial cell carcinoma of the bladder. The Journal of Urology, 177, 2347–2351.

    Article  CAS  PubMed  Google Scholar 

  • Smyth, M. J., Cretney, E., Kershaw, M. H., & Hayakawa, Y. (2004). Cytokines in cancer immunity and immunotherapy. Immunological Reviews, 202, 275–293.

    Article  CAS  PubMed  Google Scholar 

  • Sobek, V., Birkner, N., Falk, I., Wurch, A., Kirschning, C. J., Wagner, H., Wallich, R., Lamers, M. C., & Simon, M. M. (2004). Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease. Arthritis Research & Therapy, 6, R433–R446.

    Article  CAS  Google Scholar 

  • Song, D. H., & Lee, J. O. (2012). Sensing of microbial molecular patterns by Toll-like receptors. Immunological Reviews, 250, 216–229.

    Article  PubMed  CAS  Google Scholar 

  • Spinetti, G., Fortunato, O., Caporali, A., Shantikumar, S., Marchetti, M., Meloni, M., Descamps, B., Floris, I., Sangalli, E., Vono, R., et al. (2013). MicroRNA-15a and microRNA-16 impair human circulating proangiogenic cell functions and are increased in the proangiogenic cells and serum of patients with critical limb ischemia. Circulation Research, 112, 335–346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sportes, C., Babb, R. R., Krumlauf, M. C., Hakim, F. T., Steinberg, S. M., Chow, C. K., Brown, M. R., Fleisher, T. A., Noel, P., Maric, I., et al. (2010). Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. Clinical Cancer Research: Official Journal of the American Association for Cancer Research, 16, 727–735.

    Article  CAS  Google Scholar 

  • Spranger, S., Javorovic, M., Burdek, M., Wilde, S., Mosetter, B., Tippmer, S., Bigalke, I., Geiger, C., Schendel, D. J., & Frankenberger, B. (2010). Generation of Th1-polarizing dendritic cells using the TLR7/8 agonist CL075. Journal of Immunology, 185, 738–747.

    Article  CAS  Google Scholar 

  • Squadrito, M. L., & De Palma, M. (2011). Macrophage regulation of tumor angiogenesis: Implications for cancer therapy. Molecular Aspects of Medicine, 32, 123–145.

    Article  CAS  PubMed  Google Scholar 

  • Squadrito, M. L., Pucci, F., Magri, L., Moi, D., Gilfillan, G. D., Ranghetti, A., Casazza, A., Mazzone, M., Lyle, R., Naldini, L., et al. (2012). miR-511-3p modulates genetic programs of tumor-associated macrophages. Cell Reports, 1, 141–154.

    Article  CAS  PubMed  Google Scholar 

  • Squadrito, M. L., Etzrodt, M., De Palma, M., & Pittet, M. J. (2013). MicroRNA-mediated control of macrophages and its implications for cancer. Trends in Immunology, 34, 350–359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinestel, K., Eder, S., Schrader, A. J., & Steinestel, J. (2014). Clinical significance of epithelial-mesenchymal transition. Clinical and Translational Medicine, 3, 17.

    Article  PubMed  PubMed Central  Google Scholar 

  • Steinman, R. M., & Cohn, Z. A. (1973). Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. The Journal of Experimental Medicine, 137, 1142–1162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sutmuller, R. P., den Brok, M. H., Kramer, M., Bennink, E. J., Toonen, L. W., Kullberg, B. J., Joosten, L. A., Akira, S., Netea, M. G., & Adema, G. J. (2006). Toll-like receptor 2 controls expansion and function of regulatory T cells. The Journal of Clinical Investigation, 116, 485–494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki, A., Leland, P., Joshi, B. H., & Puri, R. K. (2015). Targeting of IL-4 and IL-13 receptors for cancer therapy. Cytokine, 75, 79–88.

    Article  CAS  PubMed  Google Scholar 

  • Szczepanski, M. J., Czystowska, M., Szajnik, M., Harasymczuk, M., Boyiadzis, M., Kruk-Zagajewska, A., Szyfter, W., Zeromski, J., & Whiteside, T. L. (2009). Triggering of Toll-like receptor 4 expressed on human head and neck squamous cell carcinoma promotes tumor development and protects the tumor from immune attack. Cancer Research, 69, 3105–3113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szeimies, R. M., Bichel, J., Ortonne, J. P., Stockfleth, E., Lee, J., & Meng, T. C. (2008). A phase II dose-ranging study of topical resiquimod to treat actinic keratosis. The British Journal of Dermatology, 159, 205–210.

    Article  CAS  PubMed  Google Scholar 

  • Taganov, K. D., Boldin, M. P., Chang, K. J., & Baltimore, D. (2006). NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proceedings of the National Academy of Sciences of the United States of America, 103, 12481–12486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka, S., Louis, D. N., Curry, W. T., Batchelor, T. T., & Dietrich, J. (2013). Diagnostic and therapeutic avenues for glioblastoma: No longer a dead end? Nature Reviews. Clinical Oncology, 10, 14–26.

    Article  CAS  PubMed  Google Scholar 

  • Taylor, M. W., & Feng, G. S. (1991). Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 5, 2516–2522.

    CAS  Google Scholar 

  • Tekpli, X., Landvik, N. E., Anmarkud, K. H., Skaug, V., Haugen, A., & Zienolddiny, S. (2013). DNA methylation at promoter regions of interleukin 1B, interleukin 6, and interleukin 8 in non-small cell lung cancer. Cancer Immunology, Immunotherapy, 62, 337–345.

    Article  CAS  PubMed  Google Scholar 

  • Thompson, J. A., Kuzel, T., Drucker, B. J., Urba, W. J., & Bukowski, R. M. (2009). Safety and efficacy of PF-3512676 for the treatment of stage IV renal cell carcinoma: An open-label, multicenter phase I/II study. Clinical Genitourinary Cancer, 7, E58–E65.

    Article  CAS  PubMed  Google Scholar 

  • Thorne, S. H. (2013). The role of GM-CSF in enhancing immunotherapy of cancer. Immunotherapy, 5, 817–819.

    Article  CAS  PubMed  Google Scholar 

  • Tomai, M. A., Miller, R. L., Lipson, K. E., Kieper, W. C., Zarraga, I. E., & Vasilakos, J. P. (2007). Resiquimod and other immune response modifiers as vaccine adjuvants. Expert Review of Vaccines, 6, 835–847.

    Article  CAS  PubMed  Google Scholar 

  • Trang, P., Wiggins, J. F., Daige, C. L., Cho, C., Omotola, M., Brown, D., Weidhaas, J. B., Bader, A. G., & Slack, F. J. (2011). Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Molecular Therapy: The Journal of the American Society of Gene Therapy, 19, 1116–1122.

    Article  CAS  Google Scholar 

  • Tremblay, M. M., Bilal, M. Y., & Houtman, J. C. (2014). Prior TLR5 induction in human T cells results in a transient potentiation of subsequent TCR-induced cytokine production. Molecular Immunology, 57, 161–170.

    Article  CAS  PubMed  Google Scholar 

  • Trepiakas, R., Pedersen, A. E., Met, O., & Svane, I. M. (2009). Addition of interferon-alpha to a standard maturation cocktail induces CD38 up-regulation and increases dendritic cell function. Vaccine, 27, 2213–2219.

    Article  CAS  PubMed  Google Scholar 

  • Ueda, R., Kohanbash, G., Sasaki, K., Fujita, M., Zhu, X., Kastenhuber, E. R., McDonald, H. A., Potter, D. M., Hamilton, R. L., Lotze, M. T., et al. (2009). Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proceedings of the National Academy of Sciences of the United States of America, 106, 10746–10751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vacchelli, E., Eggermont, A., Sautes-Fridman, C., Galon, J., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2013). Trial watch: Toll-like receptor agonists for cancer therapy. Oncoimmunology, 2, e25238.

    Article  PubMed  PubMed Central  Google Scholar 

  • Volinia, S., Calin, G. A., Liu, C. G., Ambs, S., Cimmino, A., Petrocca, F., Visone, R., Iorio, M., Roldo, C., Ferracin, M., et al. (2006). A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the United States of America, 103, 2257–2261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Voronov, E., Carmi, Y., & Apte, R. N. (2014). The role IL-1 in tumor-mediated angiogenesis. Frontiers in Physiology, 5, 114.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang, J. H., Manning, B. J., Wu, Q. D., Blankson, S., Bouchier-Hayes, D., & Redmond, H. P. (2003). Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism. Journal of Immunology (Baltimore, Md.: 1950), 170, 795–804.

    Article  CAS  Google Scholar 

  • Wang, P., Xue, Y., Han, Y., Lin, L., Wu, C., Xu, S., Jiang, Z., Xu, J., Liu, Q., & Cao, X. (2014). The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science (New York, NY), 344, 310–313.

    Article  CAS  Google Scholar 

  • Wargo, J. A., Reuben, A., Cooper, Z. A., Oh, K. S., & Sullivan, R. J. (2015). Immune effects of chemotherapy, radiation, and targeted therapy and opportunities for combination with immunotherapy. Seminars in Oncology, 42, 601–616.

    Article  CAS  PubMed  Google Scholar 

  • Weichhart, T., Haidinger, M., Katholnig, K., Kopecky, C., Poglitsch, M., Lassnig, C., Rosner, M., Zlabinger, G. J., Hengstschlager, M., Muller, M., et al. (2011). Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells. Blood, 117, 4273–4283.

    Article  CAS  PubMed  Google Scholar 

  • Weihrauch, M. R., Ansen, S., Jurkiewicz, E., Geisen, C., Xia, Z., Anderson, K. S., Gracien, E., Schmidt, M., Wittig, B., Diehl, V., et al. (2005). Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer. Clinical Cancer Research: Official Journal of the American Association for Cancer Research, 11, 5993–6001.

    Article  CAS  Google Scholar 

  • Wheeler, C. J., Black, K. L., Liu, G., Mazer, M., Zhang, X. X., Pepkowitz, S., Goldfinger, D., Ng, H., Irvin, D., & Yu, J. S. (2008). Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Research, 68, 5955–5964.

    Article  CAS  PubMed  Google Scholar 

  • Willingham, A. T., Orth, A. P., Batalov, S., Peters, E. C., Wen, B. G., Aza-Blanc, P., Hogenesch, J. B., & Schultz, P. G. (2005). A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science (New York, NY), 309, 1570–1573.

    Article  CAS  Google Scholar 

  • Wingender, G., Garbi, N., Schumak, B., Jungerkes, F., Endl, E., von Bubnoff, D., Steitz, J., Striegler, J., Moldenhauer, G., Tuting, T., et al. (2006). Systemic application of CpG-rich DNA suppresses adaptive T cell immunity via induction of IDO. European Journal of Immunology, 36, 12–20.

    Article  CAS  PubMed  Google Scholar 

  • Wittig, B., Schmidt, M., Scheithauer, W., & Schmoll, H. J. (2015). MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside. Critical Reviews in Oncology/Hematology, 94, 31–44.

    Article  PubMed  Google Scholar 

  • Wu, A., Oh, S., Gharagozlou, S., Vedi, R. N., Ericson, K., Low, W. C., Chen, W., & Ohlfest, J. R. (2007). In vivo vaccination with tumor cell lysate plus CpG oligodeoxynucleotides eradicates murine glioblastoma. Journal of Immunotherapy, 30, 789–797.

    Article  CAS  PubMed  Google Scholar 

  • Wu, M. F., Yang, J., Xiang, T., Shi, Y. Y., & Liu, L. J. (2014). miR-21 targets Fas ligand-mediated apoptosis in breast cancer cell line MCF-7. Journal of Huazhong University of Science and Technology. Medical Sciences, 34, 190–194.

    Article  CAS  Google Scholar 

  • Xiang, T., Long, H., He, L., Han, X., Lin, K., Liang, Z., Zhuo, W., Xie, R., & Zhu, B. (2015). Interleukin-17 produced by tumor microenvironment promotes self-renewal of CD133+ cancer stem-like cells in ovarian cancer. Oncogene, 34, 165–176.

    Article  CAS  PubMed  Google Scholar 

  • Xie, G., Yao, Q., Liu, Y., Du, S., Liu, A., Guo, Z., Sun, A., Ruan, J., Chen, L., Ye, C., et al. (2012). IL-6-induced epithelial-mesenchymal transition promotes the generation of breast cancer stem-like cells analogous to mammosphere cultures. International Journal of Oncology, 40, 1171–1179.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong, Z., & Ohlfest, J. R. (2011). Topical imiquimod has therapeutic and immunomodulatory effects against intracranial tumors. Journal of Immunotherapy, 34, 264–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu, B., Bai, B., Sha, S., Yu, P., An, Y., Wang, S., Kong, X., Liu, C., Wei, N., Feng, Q., et al. (2014). Interleukin-1beta induces autophagy by affecting calcium homeostasis and trypsinogen activation in pancreatic acinar cells. International Journal of Clinical and Experimental Pathology, 7, 3620–3631.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yanaihara, N., Caplen, N., Bowman, E., Seike, M., Kumamoto, K., Yi, M., Stephens, R. M., Okamoto, A., Yokota, J., Tanaka, T., et al. (2006). Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell, 9, 189–198.

    Article  CAS  PubMed  Google Scholar 

  • Yang, J. C., Topalian, S. L., Parkinson, D., Schwartzentruber, D. J., Weber, J. S., Ettinghausen, S. E., White, D. E., Steinberg, S. M., Cole, D. J., Kim, H. I., et al. (1994). Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: An interim report. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 12, 1572–1576.

    CAS  Google Scholar 

  • Yang, Y. P., Chien, Y., Chiou, G. Y., Cherng, J. Y., Wang, M. L., Lo, W. L., Chang, Y. L., Huang, P. I., Chen, Y. W., Shih, Y. H., et al. (2012). Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. Biomaterials, 33, 1462–1476.

    Article  CAS  PubMed  Google Scholar 

  • Yee, C., Thompson, J. A., Byrd, D., Riddell, S. R., Roche, P., Celis, E., & Greenberg, P. D. (2002). Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: In vivo persistence, migration, and antitumor effect of transferred T cells. Proceedings of the National Academy of Sciences of the United States of America, 99, 16168–16173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yeung, Y. T., McDonald, K. L., Grewal, T., & Munoz, L. (2013). Interleukins in glioblastoma pathophysiology: Implications for therapy. British Journal of Pharmacology, 168, 591–606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoneda, K., Sugimoto, K., Shiraki, K., Tanaka, J., Beppu, T., Fuke, H., Yamamoto, N., Masuya, M., Horie, R., Uchida, K., et al. (2008). Dual topology of functional toll-like receptor 3 expression in human hepatocellular carcinoma: Differential signaling mechanisms of TLR3-induced NF-kappaB activation and apoptosis. International Journal of Oncology, 33, 929–936.

    CAS  PubMed  Google Scholar 

  • Zarate, R., Boni, V., Bandres, E., & Garcia-Foncillas, J. (2012). MiRNAs and LincRNAs: Could they be considered as biomarkers in colorectal cancer? International Journal of Molecular Sciences, 13, 840–865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zarogoulidis, P., Lampaki, S., Yarmus, L., Kioumis, I., Pitsiou, G., Katsikogiannis, N., Hohenforst-Schmidt, W., Li, Q., Huang, H., Sakkas, A., et al. (2014). Interleukin-7 and interleukin-15 for cancer. Journal of Cancer, 5, 765–773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zent, C. S., Smith, B. J., Ballas, Z. K., Wooldridge, J. E., Link, B. K., Call, T. G., Shanafelt, T. D., Bowen, D. A., Kay, N. E., Witzig, T. E., et al. (2012). Phase I clinical trial of CpG oligonucleotide 7909 (PF-03512676) in patients with previously treated chronic lymphocytic leukemia. Leukemia & Lymphoma, 53, 211–217.

    Article  CAS  Google Scholar 

  • Zhan, Z., Xie, X., Cao, H., Zhou, X., Zhang, X. D., Fan, H., & Liu, Z. (2014). Autophagy facilitates TLR4- and TLR3-triggered migration and invasion of lung cancer cells through the promotion of TRAF6 ubiquitination. Autophagy, 10, 257–268.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, X., Gejman, R., Mahta, A., Zhong, Y., Rice, K. A., Zhou, Y., Cheunsuchon, P., Louis, D. N., & Klibanski, A. (2010). Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression. Cancer Research, 70, 2350–2358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, M., Liu, Q., Mi, S., Liang, X., Zhang, Z., Su, X., Liu, J., Chen, Y., Wang, M., Zhang, Y., et al. (2011a). Both miR-17-5p and miR-20a alleviate suppressive potential of myeloid-derived suppressor cells by modulating STAT3 expression. Journal of Immunology, 186, 4716–4724.

    Article  CAS  Google Scholar 

  • Zhang, Y., Luo, F., Cai, Y., Liu, N., Wang, L., Xu, D., & Chu, Y. (2011b). TLR1/TLR2 agonist induces tumor regression by reciprocal modulation of effector and regulatory T cells. Journal of Immunology (Baltimore, Md.: 1950), 186, 1963–1969.

    Article  CAS  Google Scholar 

  • Zhang, C., Bai, D. S., Huang, X. Y., Shi, G. M., Ke, A. W., Yang, L. X., Yang, X. R., Zhou, J., & Fan, J. (2013a). Prognostic significance of capn4 overexpression in intrahepatic cholangiocarcinoma. PloS One, 8, e54619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y., Wang, Z., & Gemeinhart, R. A. (2013b). Progress in microRNA delivery. Journal of Controlled Release: Official Journal of the Controlled Release Society, 172, 962–974.

    Article  CAS  Google Scholar 

  • Zhang, Y., Lin, A., Sui, Q., Zhang, C., Tian, Z., & Zhang, J. (2014a). Phosphorothioate modification of the TLR9 ligand CpG ODN inhibits poly(I:C)-induced apoptosis of hepatocellular carcinoma by entry blockade. Cancer Letters, 355, 76–84.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Y., Luo, F., Li, A., Qian, J., Yao, Z., Feng, X., & Chu, Y. (2014b). Systemic injection of TLR1/2 agonist improves adoptive antigen-specific T cell therapy in glioma-bearing mice. Clinical Immunology, 154, 26–36.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, N., Li, X., He, X., Qiu, Y., Zhu, L., & Qi, F. (2013). Interleukin-15 gene therapy and the mammalian target of rapamycin inhibitor everolimus inhibit the growth of metastatic breast cancer. The Journal of Gene Medicine, 15, 366–374.

    Article  CAS  PubMed  Google Scholar 

  • Zheng, Y., Xiong, S., Jiang, P., Liu, R., Liu, X., Qian, J., Zheng, X., & Chu, Y. (2012). Glucocorticoids inhibit lipopolysaccharide-mediated inflammatory response by downregulating microRNA-155: A novel anti-inflammation mechanism. Free Radical Biology & Medicine, 52, 1307–1317.

    Article  CAS  Google Scholar 

  • Zhong, G., Cheng, X., Long, H., He, L., Qi, W., Xiang, T., Zhao, Z., & Zhu, B. (2013). Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma. Journal of Translational Medicine, 11, 71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou, H., Hu, H., & Lai, M. (2010). Non-coding RNAs and their epigenetic regulatory mechanisms. Biology of the Cell/Under the Auspices of the European Cell Biology Organization, 102, 645–655.

    Article  CAS  PubMed  Google Scholar 

  • Zhu, X., Nishimura, F., Sasaki, K., Fujita, M., Dusak, J. E., Eguchi, J., Fellows-Mayle, W., Storkus, W. J., Walker, P. R., Salazar, A. M., et al. (2007). Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor models. Journal of Translational Medicine, 5, 10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhuang, G., Meng, C., Guo, X., Cheruku, P. S., Shi, L., Xu, H., Li, H., Wang, G., Evans, A. R., Safe, S., et al. (2012). A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation. Circulation, 125, 2892–2903.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, No.138, Yi Xue Yuan Rd., mail box 226, Shanghai, 200032, People’s Republic of China

    Ronghua Liu, Xiaoming Liu, Luman Wang, Jiao Yang, Yuting Deng, Enyu Huang, Jiawen Qian, Zhou Lu, Xuechao Jiang, Dan Zhang & Yiwei Chu

  2. Biotherapy Research Center, Fudan University, Shanghai, 200032, China

    Ronghua Liu, Feifei Luo, Luman Wang, Jiao Yang, Yuting Deng, Enyu Huang, Jiawen Qian, Zhou Lu, Xuechao Jiang, Dan Zhang & Yiwei Chu

  3. Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai, China

    Feifei Luo

  4. Department of Dermatology, Shenzhen Hospital, Peking University, Shenzhen, Guangdong, 518036, China

    Xiaoming Liu

Authors
  1. Ronghua Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feifei Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaoming Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luman Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuting Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Enyu Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jiawen Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhou Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xuechao Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yiwei Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yiwei Chu .

Editor information

Editors and Affiliations

  1. Dept. of Immunology, Cancer Inst & Hospi, Chinese Acad Med & Peking Med Coll, Beijing, China

    Shuren Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Liu, R. et al. (2016). Biological Response Modifier in Cancer Immunotherapy. In: Zhang, S. (eds) Progress in Cancer Immunotherapy. Advances in Experimental Medicine and Biology, vol 909. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7555-7_2

Download citation

Publish with us

Policies and ethics

Search

Navigation