The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy
Abstract
:1. Introduction
2. Cutaneous Melanoma
2.1. MiRNAs in Cutaneous Melanoma
Upstream Stimulation | MiRNAs | Downstream Regulation | Functions | Experimental Methods | Literatures |
---|---|---|---|---|---|
Cancer-associated fibroblasts (CAFs) | |||||
TGF-β1 treatment | miR-21 ↑ | Direct target: SMAD7 ↑ TGF-β signaling ↑ FSP1 expression ↑ | Formation of CAFs | In melanoma cell lines + murine models | [19] |
/ | miR-211 ↑ | Direct target: IGF2R expression ↓ MAPK signaling ↑ Pro-inflammatory genes: IL1-β, IL-6, IL-8, CXCL1 and CXCL2 expression ↑ | Formation of CAFs | In melanoma cell lines + murine models | [20] |
/ | miR-210 and miR-155 ↑ | Glycolysis metabolism ↑ Oxidative phosphorylation ↓ | Formation of CAFs | Only in melanoma cell lines | [21] |
/ | miR-155-5p ↑ | Direct target: SOCS1 ↓ JAK2/STAT3 signaling ↑ Proangiogenic factors: VEGFa, FGF2, and MMP9 ↑ | Formation and the proangiogenic switch of CAFs | In melanoma cell lines + murine models | [22] |
Dendritic cells (DCs) | |||||
Pro-inflammatory stimulation of lipopolysaccharide (LPS) | miR-9 ↑ | Direct target: PCGF6 ↓ Pro-inflammatory cytokines: IL-12p40, IL-6, TNFa, and IL-12p70 ↑ | Increasing activation of T cells | In melanoma cell lines + murine models | [23] |
/ | miR-22 ↑ | Direct target: p38 ↓ MAPK signaling ↓ IL-10 expression ↓ | Inhibiting Th17 cells differentiation | In melanoma cell lines + murine models | [24] |
TGF-β treatment | miR-27a ↑ | Direct target: TAB3, p38 MAPK, MAP2K4 and MAP2K7 ↓ NF-kB and MAPK–JNK signaling ↓ (NF-a, IL-1b, IL-6, IL-12 and IL-23 ↓) | Inhibiting the differentiation of Th1 and Th17 cells | In melanoma cell lines + murine models | [25] |
/ | miR-128 ↑ | Direct target: p38 ↓ MAPK signaling ↓ (Expression of IL-6 and IL-10 ↑, IL-12 ↓) | Enhancing anti-tumor ability of DCs | In melanoma cell lines + murine models | [26] |
Macrophages | |||||
/ | miR-21 ↑ | Direct target: STAT1 ↓ IFN-γ-induced STAT1 signaling ↓ | Inhibiting polarization of M1 macrophages and decreasing the anti-tumor ability of macrophages | In melanoma cell lines + murine models | [27] |
/ | GZMB, CXCL10, IL-10 ↓ | Decreasing cytotoxicity of CD8+ T cells and improving angiogenesis of melanoma cells | In melanoma cell lines + murine models | [28] | |
Activation of CSF1-ETS2 pathway | miR-21 and miR-29a ↑ | miR-21 targets: Pdcd4, Spry1 and Timp3 ↓ miR-29a targets: Col4a2, Sparc and Timp3 ↓ | Inhibiting polarization of M1 macrophages and promoting tumor cell proliferation and angiogenesis | In melanoma cell lines + murine models | [29] |
/ | miR-125b-5p ↑ | Direct targets: LIPA ↓ (CCL1, CCL2, and IL-1β expression ↑) | Reinforcing the polarization of M1 macrophages and prolonging the survival of macrophages | Only in melanoma cell lines | [30,31,32] |
Activation of NF-κB signaling | miR-146 ↑ | TRAF6, IRAK1, and IRAK2An NF-kappaB ↓ | Promoting polarization of M1 macrophages and immune response of macrophages | In melanoma cell lines + murine models | [30,33,34] |
/ | miR-155 ↑ | IFN-inducible genes ↑ | Promoting the activation of M2 macrophages | In melanoma cell lines + murine models | [35,36,37] |
Natural killer cells (NKs) | |||||
/ | miR-34a/c ↑ | ULBP2 expression ↓ NKG2D-dependent signaling ↓ | Promoting the recognition and suppression of tumors in NK cells | Only in melanoma cell lines | [38] |
/ | miR-155 ↑ | IFN-c and granzyme B production and NKG2D expression ↑ | Decreasing the sensitivity of melanoma cells to NK cells cytolysis | Only in melanoma cell lines | [39] |
/ | miR-200a-5p ↑ | Direct target: TAP1 expression ↓ HLA-I pathway ↓ | Increasing the NK cells recognition to melanoma cells | Only in melanoma cell lines | [40] |
Myeloid derived suppressor cells (MDSCs) | |||||
Induction of TGF-β 1 | miR-494 ↑ | Direct target: PTEN ↓ Akt pathways ↑ Levels of metalloproteinases (MMP2, MMP13, and MMP14) ↑ | Increasing the activity of MDSCs as well as tumor cell invasion and metastasis | In melanoma cell lines + murine models | [41] |
/ | miR-146b, miR-155, miR-125a/b, miR-164a, miR-100, let-7e and miR-99b ↑ | STAT3 downstream signaling pathways ↓ | Polarization and T cells-inhibiting functions of MDSCs | In melanoma cell lines + murine models | [18] |
T cells | |||||
Pro-inflammatory stimulation of lipopolysaccharide (LPS) | miR-9 ↑ | Direct target: PCGF6 ↓ pro-inflammatory cytokines IL-12p40, IL-6, TNFa, and IL-12p70 ↑ | Increasing antigen sensitivity of CD8+ OT1 T cells | In melanoma cell lines + murine models | [23] |
TCR activation and TGF-β signaling | miR-23a ↑ | Direct target: BLIMP-1 ↑ granzyme B expression ↑ | Attenuating the antitumor response of cytotoxic T cells | In melanoma cell lines + murine models | [42] |
/ | miR-26b-5p and miR-21-3p ↑ | TAP1 protein ↓ HLA class I cell surface antigens ↓ | Decreasing the recognitions of T cells | Only in melanoma cell lines | [43] |
/ | miR-28 ↑ | Targets: PD1, TIM3 and BTLA ↓ IL-2 and TNF-α ↑ | Promoting exhaustive differentiation of T cells | In melanoma cell lines + murine models | [44] |
/ | miR-30b/d ↑ | Target: GALNT7 ↓ IL-10 expression ↑ | reduction of CD3+ T cells recruitment and induction of regulatory T cells. | In melanoma cell lines + murine models | [45] |
/ | miR-210 ↑ | Targets: PTPN1, HOXA1, and TP53I11 ↓ | Increasing susceptibility of tumor cells to lysis by cytotoxic T cells | Only in melanoma cell lines | [46] |
/ | miR-30c, miR-23a, miR-4299 ↑ | Target: TNFRSF8 ↓ CD30 expression ↓ | Associating of dysfunctional immune response | Only in melanoma cell lines | [47] |
/ | miR-498 and miR-3187-3p ↑ | Targets: PTPRC (CD45) ↓ TCR signaling ↓ TNFa secretion ↓ | Reducing the functions of CD8+ T cells | Only in melanoma cell lines | [48] |
Hypoxic stress in melanoma cells and Cx43 signaling upregulation | miR-192-5p ↑ | Target: ZEB2 ↓ | Lowering cytotoxic activity of T cells | In melanoma cell lines + murine models | [49] |
/ | miR-155 ↑ | Targets: STAT5, SHIP1, SOCS1, and PTPN2 ↓ Akt and Stat5 signaling ↓ | Enhancing CD8+ T-cell antitumor responses | In melanoma cell lines + murine models | [49,50,51,52,53,54] |
2.2. MiRNAs in Immunotherapy
MiRNAs | Treatment | Regulation | Sample Size | Source | Literature |
---|---|---|---|---|---|
miR-155 | PD-(L)1 inhibitor | miR-155 was upregulated after receiving anti-PD-1 treatment, which associated with prolonged overall survival | 9 healthy donors and 13 patients | blood, tumor tissue | [53] |
miR-100-5p and miR-125-5p | PD-(L)1 inhibitor | miR-100-5p and miR-125-5p were upregulated in responding patients, which associated with prolonged overall survival | 13 no clinical benefit patients and 9 clinical benefit patients | biopsies | [16] |
miR-16-5p, miR-14-5p, and miR-20a-5p | PD-(L)1 inhibitor | The levels of miR-16-5p, miR-14-5p, and miR-20a-5p was twice higher in the responding group than non-responding group | 33 patients with malignant melanoma | serum | [17] |
exo-miRNA-532-5p and exo-miRNA-106b | PD-(L)1 inhibitor | The levels of exo-miRNA-532-5p and exo-miRNA-106b significantly decreased in patients than in healthy people (Z = −4.17 and −4.57, respectively, p < 0.0001) | 95 patients and 95 healthy donors | serum | [66] |
miR-4649-3p, miR-615-3p, and miR-1234-3p | PD-(L)1 inhibitor | MiR-4649-3p, miR-615-3p, and miR-1234-3p were significantly decreased in completing-responding patients and partial-responding patients compared with the non-responding group | 47 malignant melanoma patients | blood | [67] |
miR-34c, miR-711, miR-641, and miR-22 | CLTA-4 inhibitor | MiR-34c, miR-711, miR-641, and miR-22 were identified to be significantly associated with progression free survival (PFS) in advanced melanoma patients treated with neoadjuvant ipilimumab | 27 melanoma patients | biopsies | [68] |
miR-222 | CLTA-4 inhibitor | The expression of hsa-miR-222 in melanoma tissues of clinical benefit patients was 2.3-fold higher (p-value = 0.001) than in no-clinical benefit patients | 12 clinical benefit patients and 23 no-clinical benefit patients | tumor tissue | [69] |
2.2.1. The Involvement of miRNAs in Response, Resistance, and Side Effects of Immunotherapy with Immune Checkpoint Inhibitors
PD-(L)1 Inhibitor
CLTA-4 Inhibitor
Combination Treatment of Immune Checkpoint Inhibitors
Other Immune Checkpoint Inhibitors
Involvement of miRNAs in Drug Resistance against Immune Checkpoint Inhibitors
Role of miRNAs in Side Effects of Immune Checkpoint Immunotherapy
2.2.2. MiRNAs Associated with Other Immunotherapies
Tumor-Infiltrating Lymphocytes (Tils)
Toll-like Receptor 9 Agonist
3. MiRNAs in Immunity and Immunotherapy of Uveal (Eye) Melanoma (UM)
4. Novel miRNAs-Based Immunotherapy
5. The Delivery Strategy of miRNA-Associated Immunotherapy
5.1. Lipid Nanoparticles
5.2. Silica Nanoparticles
5.3. Gold Nanoparticles
5.4. Extracellular Vesicles
5.5. Dendrimer
5.6. Future Challenges
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Stewart, B.W.; Kleihues, P. World Cancer Report; IARC Press: Lyon, France, 2003. [Google Scholar]
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics. CA-Cancer J. Clin. 2022, 72, 7–33. [Google Scholar] [CrossRef] [PubMed]
- Lasithiotakis, K.; Leiter, U.; Kruger-Krasagakis, S.; Tosca, A.; Garbe, C. Comparative analysis of incidence and clinical features of cutaneous malignant melanoma in Crete (Greece) and southern Germany (central Baden-Wurttemberg). Br. J. Dermatol. 2006, 154, 1123–1127. [Google Scholar] [CrossRef] [PubMed]
- Allais, B.S.; Beatson, M.; Wang, H.K.; Shahbazi, S.; Bijelic, L.; Jang, S.; Venna, S. Five-year survival in patients with nodular and superficial spreading melanomas in the US population. J. Am. Acad. Dermatol. 2021, 84, 1015–1022. [Google Scholar] [CrossRef] [PubMed]
- Coit, D.G.; Thompson, J.A.; Albertini, M.R.; Barker, C.; Carson, W.E.; Contreras, C.; Daniels, G.A.; DiMaio, D.; Fields, R.C.; Fleming, M.D.; et al. Cutaneous Melanoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 2019, 17, 367–402. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sullivan, R.J.; Hodi, F.S. Melanoma Immunology and Immunotherapy. In Melanoma; Fisher, D., Bastian, B., Eds.; Springer: New York, NY, USA, 2019; pp. 1–15. [Google Scholar]
- Ralli, M.; Botticelli, A.; Visconti, I.C.; Angeletti, D.; Fiore, M.; Marchetti, P.; Lambiase, A.; de Vincentiis, M.; Greco, A. Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions. J. Immunol. Res. 2020, 2020, 9235638. [Google Scholar] [CrossRef] [PubMed]
- Czarnecka, A.M.; Bartnik, E.; Fiedorowicz, M.; Rutkowski, P. Targeted Therapy in Melanoma and Mechanisms of Resistance. Int. J. Mol. Sci. 2020, 21, 4576. [Google Scholar] [CrossRef] [PubMed]
- Chennamadhavuni, A.; Abushahin, L.; Jin, N.; Presley, C.J.; Manne, A. Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors. Front. Immunol. 2022, 13, 779691. [Google Scholar] [CrossRef]
- Kennedy, L.B.; Salama, A.K.S. A Review of Immune-Mediated Adverse Events in Melanoma. Oncol. Ther. 2019, 7, 101–120. [Google Scholar] [CrossRef] [Green Version]
- Lee, R.C.; Feinbaum, R.L.; Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993, 75, 843–854. [Google Scholar] [CrossRef]
- Wightman, B.; Ha, I.; Ruvkun, G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993, 75, 855–862. [Google Scholar] [CrossRef] [PubMed]
- Peng, Q.; Wang, J. Non-coding RNAs in melanoma: Biological functions and potential clinical applications. Mol. Ther. Oncolytics 2021, 22, 219–231. [Google Scholar] [CrossRef]
- Li, Y.; Fu, Y.; Gao, Y.; Li, H.; Ma, L.; Shu, C.; Li, N.; Ma, C. microRNA-134 inhibits melanoma growth and metastasis by negatively regulating collagen triple helix repeat containing-1 (CTHRC1). Int. J. Clin. Exp. Pathol. 2018, 11, 4319–4330. [Google Scholar]
- Yang, C.; Yan, Z.; Hu, F.; Wei, W.; Sun, Z.; Xu, W. Silencing of microRNA-517a induces oxidative stress injury in melanoma cells via inactivation of the JNK signaling pathway by upregulating CDKN1C. Cancer Cell Int. 2020, 20, 32. [Google Scholar] [CrossRef]
- Sloane, R.A.S.; White, M.G.; Witt, R.G.; Banerjee, A.; Davies, M.A.; Han, G.C.; Burton, E.; Ajami, N.; Simon, J.M.; Bernatchez, C.; et al. Identification of MicroRNA-mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes. Cancers 2021, 13, 5301. [Google Scholar] [CrossRef]
- Nakahara, S.; Fukushima, S.; Okada, E.; Morinaga, J.; Kubo, Y.; Tokuzumi, A.; Matsumoto, S.; Tsuruta-Kadohisa, M.; Kimura, T.; Kuriyama, H.; et al. MicroRNAs that predict the effectiveness of anti-PD-1 therapies in patients with advanced melanoma. J. Dermatol. Sci. 2020, 97, 77–79. [Google Scholar] [CrossRef] [PubMed]
- Huber, V.; Vallacchi, V.; Fleming, V.; Hu, X.Y.; Cova, A.; Dugo, M.; Shahaj, E.; Sulsenti, R.; Vergani, E.; Filipazzi, P.; et al. Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma. J. Clin. Investig. 2018, 128, 5505–5516. [Google Scholar] [CrossRef] [Green Version]
- Li, Q.; Zhang, D.; Wang, Y.; Sun, P.; Hou, X.; Larner, J.; Xiong, W.; Mi, J. MiR-21/Smad 7 signaling determines TGF-beta1-induced CAF formation. Sci. Rep. 2013, 3, 2038. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dror, S.; Sander, L.; Schwartz, H.; Sheinboim, D.; Barzilai, A.; Dishon, Y.; Apcher, S.; Golan, T.; Greenberger, S.; Barshack, I.; et al. Melanoma miRNA trafficking controls tumour primary niche formation. Nat. Cell Biol. 2016, 18, 1006–1017. [Google Scholar] [CrossRef] [PubMed]
- Shu, S.L.; Yang, Y.C.; Allen, C.L.; Maguire, O.; Minderman, H.; Sen, A.; Ciesielski, M.J.; Collins, K.A.; Bush, P.J.; Singh, P.; et al. Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment. Sci. Rep. 2018, 8, 12905. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, X.; Yan, T.; Huang, C.; Xu, Z.; Wang, L.; Jiang, E.; Wang, H.; Chen, Y.; Liu, K.; Shao, Z.; et al. Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway. J. Exp. Clin. Cancer Res. 2018, 37, 242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cordeiro, B.; Jeon, P.; Boukhaled, G.M.; Corrado, M.; Lapohos, O.; Roy, D.G.; Williams, K.; Jones, R.G.; Gruenheid, S.; Sagan, S.M.; et al. MicroRNA-9 Fine-Tunes Dendritic Cell Function by Suppressing Negative Regulators in a Cell-Type-Specific Manner. Cell Rep. 2020, 31, 107585. [Google Scholar] [CrossRef] [PubMed]
- Liang, X.; Liu, Y.; Mei, S.Y.; Zhang, M.M.; Xin, J.X.; Zhang, Y.; Yang, R.C. MicroRNA-22 Impairs Anti-Tumor Ability of Dendritic Cells by Targeting p38. PLoS ONE 2015, 10, e0121510. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Min, S.; Li, L.; Zhang, M.; Zhang, Y.; Liang, X.; Xie, Y.; He, Q.; Li, Y.; Sun, J.; Liu, Q.; et al. TGF-beta-associated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7. Genes Immun. 2012, 13, 621–631. [Google Scholar] [CrossRef] [PubMed]
- Liang, X.; Shangguan, W.F.; Zhang, M.M.; Mei, S.Y.; Wang, L.Y.; Yang, R.C. miR-128 enhances dendritic cell-mediated anti-tumor immunity via targeting of p38. Mol. Med. Rep. 2017, 16, 1307–1313. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, S.S.; Liu, M.; Xu, Z.B.; Li, Y.S.; Guo, H.; Ge, Y.H.; Liu, Y.X.; Zheng, D.X.; Shi, J. A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression. Oncotarget 2016, 7, 13502–13519. [Google Scholar] [CrossRef] [Green Version]
- Sahraei, M.; Chaube, B.; Liu, Y.T.; Sun, J.; Kaplan, A.; Price, N.L.; Ding, W.; Oyaghire, S.; Garcia-Milian, R.; Mehta, S.; et al. Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response. J. Clin. Investig. 2019, 129, 5518–5536. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mathsyaraja, H.; Thies, K.; Taffany, D.A.; Deighan, C.; Liu, T.; Yu, L.; Fernandez, S.A.; Shapiro, C.; Otero, J.; Timmers, C.; et al. CSF1-ETS2-induced microRNA in myeloid cells promote metastatic tumor growth. Oncogene 2015, 34, 3651–3661. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, H.M.; Kim, T.S.; Jo, E.K. MiR-146 and miR-125 in the regulation of innate immunity and inflammation. BMB Rep. 2016, 49, 311–318. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Banerjee, S.; Cui, H.C.; Xie, N.; Tan, Z.; Yang, S.Z.; Icyuz, M.; Thannickal, V.J.; Abraham, E.; Liu, G. miR-125a-5p Regulates Differential Activation of Macrophages and Inflammation. J. Biol. Chem. 2013, 288, 35428–35436. [Google Scholar] [CrossRef] [Green Version]
- Gerloff, D.; Lutzkendorf, J.; Moritz, R.K.C.; Wersig, T.; Mader, K.; Muller, L.P.; Sunderkotter, C. Melanoma-Derived Exosomal miR-125b-5p Educates Tumor Associated Macrophages (TAMs) by Targeting Lysosomal Acid Lipase A (LIPA). Cancers 2020, 12, 464. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taganov, K.D.; Boldin, M.P.; Chang, K.J.; Baltimore, D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. USA 2006, 103, 12481–12486. [Google Scholar] [CrossRef] [PubMed]
- Mann, M.; Mehta, A.; Zhao, J.L.; Lee, K.; Marinov, G.K.; Garcia-Flores, Y.; Lu, L.F.; Rudensky, A.Y.; Baltimore, D. Author Correction: An NF-kappaB-microRNA regulatory network tunes macrophage inflammatory responses. Nat. Commun. 2018, 9, 3338. [Google Scholar] [CrossRef] [PubMed]
- Rosenberg, S.A.; Dudley, M.E. Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr. Opin. Immunol. 2009, 21, 233–240. [Google Scholar] [CrossRef] [Green Version]
- Nazari-Jahantigh, M.; Wei, Y.; Noels, H.; Akhtar, S.; Zhou, Z.; Koenen, R.R.; Heyll, K.; Gremse, F.; Kiessling, F.; Grommes, J.; et al. MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages. J. Clin. Investig. 2012, 122, 4190–4202. [Google Scholar] [CrossRef] [Green Version]
- Martinez-Nunez, R.T.; Louafi, F.; Sanchez-Elsner, T. The interleukin 13 (IL-13) pathway in human macrophages is modulated by microRNA-155 via direct targeting of interleukin 13 receptor alpha1 (IL13Ralpha1). J. Biol. Chem. 2011, 286, 1786–1794. [Google Scholar] [CrossRef] [Green Version]
- Heinemann, A.; Zhao, F.; Pechlivanis, S.; Eberle, J.; Steinle, A.; Diederichs, S.; Schadendorf, D.; Paschen, A. Tumor Suppressive MicroRNAs miR-34a/c Control Cancer Cell Expression of ULBP2, a Stress-Induced Ligand of the Natural Killer Cell Receptor NKG2D. Cancer Res. 2012, 72, 460–471. [Google Scholar] [CrossRef] [Green Version]
- Trotta, R.; Chen, L.; Ciarlariello, D.; Josyula, S.; Mao, C.; Costinean, S.; Yu, L.B.; Butchar, J.P.; Tridandapani, S.; Croce, C.M.; et al. miR-155 regulates IFN-gamma production in natural killer cells. Blood 2012, 119, 3478–3485. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lazaridou, M.F.; Gonschorek, E.; Massa, C.; Friedrich, M.; Handke, D.; Mueller, A.; Jasinski-Bergner, S.; Dummer, R.; Koelblinger, P.; Seliger, B. Identification of miR-200a-5p targeting the peptide transporter TAP1 and its association with the clinical outcome of melanoma patients. Oncoimmunology 2020, 9, 1774323. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Lai, L.H.; Chen, Q.Y.; Song, Y.J.; Xu, S.; Ma, F.; Wang, X.J.; Wang, J.L.; Yu, H.; Cao, X.T.; et al. MicroRNA-494 Is Required for the Accumulation and Functions of Tumor-Expanded Myeloid-Derived Suppressor Cells via Targeting of PTEN. J. Immunol. 2012, 188, 5500–5510. [Google Scholar] [CrossRef] [Green Version]
- Lin, R.; Chen, L.; Chen, G.; Hu, C.Y.; Jiang, S.; Sevilla, J.; Wan, Y.; Sampson, J.H.; Zhu, B.; Li, Q.J. Targeting miR-23a in CD8(+) cytotoxic T lymphocytes prevents tumor-dependent immunosuppression. J. Clin. Investig. 2014, 124, 5352–5367. [Google Scholar] [CrossRef]
- Lazaridou, M.F.; Massa, C.; Handke, D.; Mueller, A.; Friedrich, M.; Subbarayan, K.; Tretbar, S.; Dummer, R.; Koelblinger, P.; Seliger, B. Identification of microRNAs Targeting the Transporter Associated with Antigen Processing TAP1 in Melanoma. J. Clin. Med. 2020, 9, 2690. [Google Scholar] [CrossRef]
- Li, Q.; Johnston, N.; Zheng, X.F.; Wang, H.M.; Zhang, X.S.; Gao, D.; Min, W.P. miR-28 modulates exhaustive differentiation of T cells through silencing programmed cell death-1 and regulating cytokine secretion. Oncotarget 2016, 7, 53735–53750. [Google Scholar] [CrossRef] [Green Version]
- Gaziel-Sovran, A.; Segura, M.F.; Di Micco, R.; Collins, M.K.; Hanniford, D.; de Miera, E.V.-S.; Rakus, J.F.; Dankert, J.F.; Shang, S.; Kerbel, R.S.; et al. miR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis. Cancer Cell 2011, 20, 104–118. [Google Scholar] [CrossRef] [Green Version]
- Noman, M.Z.; Buart, S.; Romero, P.; Ketari, S.; Janji, B.; Mari, B.; Mami-Chouaib, F.; Chouaib, S. Hypoxia-inducible miR-210 regulates the susceptibility of tumor cells to lysis by cytotoxic T cells. Cancer Res. 2012, 72, 4629–4641. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vallacchi, V.; Camisaschi, C.; Dugo, M.; Vergani, E.; Deho, P.; Gualeni, A.; Huber, V.; Gloghini, A.; Maurichi, A.; Santinami, M.; et al. microRNA Expression in Sentinel Nodes from Progressing Melanoma Patients Identifies Networks Associated with Dysfunctional Immune Response. Genes 2016, 7, 124. [Google Scholar] [CrossRef] [Green Version]
- Vignard, V.; Labbe, M.; Marec, N.; Andre-Gregoire, G.; Jouand, N.; Fonteneau, J.F.; Labarriere, N.; Fradin, D. MicroRNAs in Tumor Exosomes Drive Immune Escape in Melanoma. Cancer Immunol. Res. 2020, 8, 255–267. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tittarelli, A.; Navarrete, M.; Lizana, M.; Hofmann-Vega, F.; Salazar-Onfray, F. Hypoxic Melanoma Cells Deliver microRNAs to Dendritic Cells and Cytotoxic T Lymphocytes through Connexin-43 Channels. Int. J. Mol. Sci. 2020, 21, 7567. [Google Scholar] [CrossRef]
- Ekiz, H.A.; Huffaker, T.B.; Grossmann, A.H.; Stephens, W.Z.; Williams, M.A.; Round, J.L.; O’Connell, R.M. MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers. JCI Insight 2019, 4, e126543. [Google Scholar] [CrossRef] [Green Version]
- Huffaker, T.B.; Lee, S.H.; Tang, W.W.; Wallace, J.A.; Alexander, M.; Runtsch, M.C.; Larsen, D.K.; Thompson, J.; Ramstead, A.G.; Voth, W.P.; et al. Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade. J. Biol. Chem. 2017, 292, 18530–18541. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dudda, J.C.; Salaun, B.; Ji, Y.; Palmer, D.C.; Monnot, G.C.; Merck, E.; Boudousquie, C.; Utzschneider, D.T.; Escobar, T.M.; Perret, R.; et al. MicroRNA-155 Is Required for Effector CD8(+) T Cell Responses to Virus Infection and Cancer. Immunity 2013, 38, 742–753. [Google Scholar] [CrossRef] [Green Version]
- Martinez-Usatorre, A.; Sempere, L.F.; Carmona, S.J.; Carretero-Iglesia, L.; Monnot, G.; Speiser, D.E.; Rufer, N.; Donda, A.; Zehn, D.; Jandus, C.; et al. MicroRNA-155 Expression Is Enhanced by T-cell Receptor Stimulation Strength and Correlates with Improved Tumor Control in Melanoma. Cancer Immunol. Res. 2019, 7, 1013–1024. [Google Scholar] [CrossRef] [PubMed]
- Rupaimoole, R.; Slack, F.J. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov. 2017, 16, 203–222. [Google Scholar] [CrossRef] [PubMed]
- Cornil, I.; Theodorescu, D.; Man, S.; Herlyn, M.; Jambrosic, J.; Kerbel, R.S. Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression. Proc. Natl. Acad. Sci. USA 1991, 88, 6028–6032. [Google Scholar] [CrossRef] [Green Version]
- Dubois, B.; Bridon, J.M.; Fayette, J.; Barthélémy, C.; Banchereau, J.; Caux, C.; Brière, F. Dendritic cells directly modulate B cell growth and differentiation. J. Leukoc. Biol. 1999, 66, 224–230. [Google Scholar] [CrossRef]
- Gerosa, F.; Baldani-Guerra, B.; Nisii, C.; Marchesini, V.; Carra, G.; Trinchieri, G. Reciprocal activating interaction between natural killer cells and dendritic cells. J. Exp. Med. 2002, 195, 327–333. [Google Scholar] [CrossRef] [PubMed]
- Merad, M.; Manz, M.G. Dendritic cell homeostasis. Blood 2009, 113, 3418–3427. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Winzler, C.; Rovere, P.; Rescigno, M.; Granucci, F.; Penna, G.; Adorini, L.; Zimmermann, V.S.; Davoust, J.; Ricciardi-Castagnoli, P. Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J. Exp. Med. 1997, 185, 317–328. [Google Scholar] [CrossRef] [Green Version]
- Lu, C.M.; Huang, X.; Zhang, X.X.; Roensch, K.; Cao, Q.; Nakayama, K.I.; Blazar, B.R.; Zeng, Y.; Zhou, X.Z. miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27(kip1), KPC1, and SOCS-1. Blood 2011, 117, 4293–4303. [Google Scholar] [CrossRef] [Green Version]
- Rodriguez, A.; Vigorito, E.; Clare, S.; Warren, M.V.; Couttet, P.; Soond, D.R.; van Dongen, S.; Grocock, R.J.; Das, P.P.; Miska, E.A.; et al. Requirement of bic/microRNA-155 for normal immune function. Science 2007, 316, 608–611. [Google Scholar] [CrossRef] [Green Version]
- Chaudhuri, A.A.; So, A.Y.; Sinha, N.; Gibson, W.S.; Taganov, K.D.; O’Connell, R.M.; Baltimore, D. MicroRNA-125b potentiates macrophage activation. J. Immunol. 2011, 187, 5062–5068. [Google Scholar] [CrossRef] [Green Version]
- Mondal, P.; Kaur, B.; Natesh, J.; Meeran, S.M. The emerging role of miRNA in the perturbation of tumor immune microenvironment in chemoresistance: Therapeutic implications. Semin. Cell Dev. Biol. 2022, 124, 99–113. [Google Scholar] [CrossRef]
- Nguyen, M.H.T.; Luo, Y.H.; Li, A.L.; Tsai, J.C.; Wu, K.L.; Chung, P.J.; Ma, N.H. miRNA as a Modulator of Immunotherapy and Immune Response in Melanoma. Biomolecules 2021, 11, 1648. [Google Scholar] [CrossRef] [PubMed]
- Wolchok, J.D.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Rutkowski, P.; Lao, C.D.; Cowey, C.L.; Schadendorf, D.; Wagstaff, J.; Dummer, R.; et al. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. J. Clin. Oncol. 2022, 40, 127–137. [Google Scholar] [CrossRef] [PubMed]
- Li, T.D.; Long, S.P.; Gu, M.L.; Guo, J.; Liu, Y.; Zhang, W.W.; Deng, A.M. Serum exosomal microRNAs as potent circulating biomarkers for melanoma. Melanoma Res. 2018, 28, 295–303. [Google Scholar]
- Bustos, M.A.; Gross, R.; Rahimzadeh, N.; Cole, H.; Tran, L.T.; Tran, K.D.; Takeshima, L.; Stern, S.L.; O’Day, S.; Hoon, D.S.B. A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients. Cancers 2020, 12, 3361. [Google Scholar] [CrossRef] [PubMed]
- Tarhini, A.; Vallabhaneni, P.; Floros, T.; LaFramboise, W.A.; Benos, P.V.; dos Santos, L.S. A tumor and immune related miRNA signature predicts progression-free survival of melanoma patients treated with ipilimumab. Cancer Res. 2016, 76, 473. [Google Scholar] [CrossRef]
- Galore-Haskel, G.; Nemlich, Y.; Greenberg, E.; Ashkenazi, S.; Hakim, M.; Itzhaki, O.; Shoshani, N.; Shapira-Fromer, R.; Ben-Ami, E.; Ofek, E.; et al. A novel immune resistance mechanism of melanoma cells controlled by the ADAR1 enzyme. Oncotarget 2015, 6, 28999–29015. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fan, J.S.; Yin, Z.Y.; Xu, J.J.; Wu, F.; Huang, Q.; Yang, L.; Jin, Y.; Yang, G.H. Circulating microRNAs predict the response to anti-PD-1 therapy in non-small cell lung cancer. Genomics 2020, 112, 2063–2071. [Google Scholar] [CrossRef] [PubMed]
- Soleimani, M.; Thi, M.; Saxena, N.; Eigl, B.J.; Khalaf, D.J.; Chi, K.N.; Kollmannsberger, C.K.; Nappi, L. Plasma exosome microRNA-155 expression in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors: A potential biomarker of response to systemic therapy. J. Clin. Oncol. 2021, 39, 4570. [Google Scholar] [CrossRef]
- Ledford, H. Melanoma drug wins US approval. Nature 2011, 471, 561. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N. Engl. J. Med. 2015, 373, 23–34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vesely, M.D.; Kershaw, M.H.; Schreiber, R.D.; Smyth, M.J. Natural Innate and Adaptive Immunity to Cancer. Annu. Rev. Immunol. 2011, 29, 235–271. [Google Scholar] [CrossRef]
- Ngiow, S.F.; von Scheidt, B.; Akiba, H.; Yagita, H.; Teng, M.W.; Smyth, M.J. Anti-TIM3 antibody promotes T cell IFN-gamma-mediated antitumor immunity and suppresses established tumors. Cancer Res. 2011, 71, 3540–3551. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Woo, S.R.; Turnis, M.E.; Goldberg, M.V.; Bankoti, J.; Selby, M.; Nirschl, C.J.; Bettini, M.L.; Gravano, D.M.; Vogel, P.; Liu, C.L.; et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012, 72, 917–927. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Workman, C.J.; Cauley, L.S.; Kim, I.J.; Blackman, M.A.; Woodland, D.L.; Vignali, D.A. Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo. J. Immunol. 2004, 172, 5450–5455. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, L.; Wang, H.; Xu, K.; Liu, X.; He, Y.; Wei, P. Update on lymphocyte-activation gene 3 (LAG-3) in cancers: From biological properties to clinical applications. Chin. Med. J. 2022, 135, 1203–1212. [Google Scholar] [CrossRef] [PubMed]
- Tawbi, H.A.; Schadendorf, D.; Lipson, E.J.; Ascierto, P.A.; Matamala, L.; Castillo Gutiérrez, E.; Rutkowski, P.; Gogas, H.J.; Lao, C.D.; De Menezes, J.J.; et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N. Engl. J. Med. 2022, 386, 24–34. [Google Scholar] [CrossRef] [PubMed]
- Yang, J.; Liu, R.; Deng, Y.; Qian, J.; Lu, Z.; Wang, Y.; Zhang, D.; Luo, F.; Chu, Y. MiR-15a/16 deficiency enhances anti-tumor immunity of glioma-infiltrating CD8+ T cells through targeting mTOR. Int. J. Cancer 2017, 141, 2082–2092. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stagg, J.; Smyth, M.J. Extracellular adenosine triphosphate and adenosine in cancer. Oncogene 2010, 29, 5346–5358. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Turiello, R.; Capone, M.; Morretta, E.; Monti, M.C.; Madonna, G.; Azzaro, R.; Del Gaudio, P.; Simeone, E.; Sorrentino, A.; Ascierto, P.A.; et al. Exosomal CD73 from serum of patients with melanoma suppresses lymphocyte functions and is associated with therapy resistance to anti-PD-1 agents. J. Immunother. Cancer 2022, 10, e004043. [Google Scholar] [CrossRef] [PubMed]
- Gao, Z.; Wang, L.; Song, Z.; Ren, M.; Yang, Y.; Li, J.; Shen, K.; Li, Y.; Ding, Y.; Yang, Y.; et al. Intratumoral CD73: An immune checkpoint shaping an inhibitory tumor microenvironment and implicating poor prognosis in Chinese melanoma cohorts. Front. Immunol. 2022, 13, 954039. [Google Scholar] [CrossRef] [PubMed]
- Stagg, J.; Divisekera, U.; McLaughlin, N.; Sharkey, J.; Pommey, S.; Denoyer, D.; Dwyer, K.M.; Smyth, M.J. Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc. Natl. Acad. Sci. USA 2010, 107, 1547–1552. [Google Scholar] [CrossRef] [PubMed]
- Monteiro, I.; Vigano, S.; Faouzi, M.; Treilleux, I.; Michielin, O.; Ménétrier-Caux, C.; Caux, C.; Romero, P.; de Leval, L. CD73 expression and clinical significance in human metastatic melanoma. Oncotarget 2018, 9, 26659–26669. [Google Scholar] [CrossRef] [Green Version]
- Passarelli, A.; Tucci, M.; Mannavola, F.; Felici, C.; Silvestris, F. The metabolic milieu in melanoma: Role of immune suppression by CD73/adenosine. Tumor. Biol. 2019, 41, 1010428319837138. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Allard, B.; Pommey, S.; Smyth, M.J.; Stagg, J. Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs. Clin. Cancer Res. 2013, 19, 5626–5635. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xie, M.; Qin, H.; Luo, Q.; Huang, Q.; He, X.; Yang, Z.; Lan, P.; Lian, L. MicroRNA-30a regulates cell proliferation and tumor growth of colorectal cancer by targeting CD73. BMC Cancer 2017, 17, 305. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, N.; Xiang, X.; Chen, K.; Liu, P.; Zhu, A. Targeting of NT5E by miR-30b and miR-340 attenuates proliferation, invasion and migration of gallbladder carcinoma. Biochimie 2018, 146, 56–67. [Google Scholar] [CrossRef] [PubMed]
- Bonnin, N.; Armandy, E.; Carras, J.; Ferrandon, S.; Battiston-Montagne, P.; Aubry, M.; Guihard, S.; Meyronet, D.; Foy, J.P.; Saintigny, P.; et al. MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma. Oncotarget 2016, 7, 44023–44038. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, F.; Luo, Y.; Shao, Z.; Xu, L.; Liu, X.; Niu, Y.; Shi, J.; Sun, X.; Liu, Y.; Ding, Y.; et al. MicroRNA-187, a downstream effector of TGFβ pathway, suppresses Smad-mediated epithelial-mesenchymal transition in colorectal cancer. Cancer Lett. 2016, 373, 203–213. [Google Scholar] [CrossRef]
- Ikeda, Y.; Tanji, E.; Makino, N.; Kawata, S.; Furukawa, T. MicroRNAs associated with mitogen-activated protein kinase in human pancreatic cancer. Mol. Cancer Res. 2012, 10, 259–269. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Caporali, S.; Amaro, A.; Levati, L.; Alvino, E.; Lacal, P.M.; Mastroeni, S.; Ruffini, F.; Bonmassar, L.; Cappellini, G.C.A.; Felli, N.; et al. miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A. J. Exp. Clin. Cancer Res. 2019, 38, 272. [Google Scholar] [CrossRef] [PubMed]
- Choe, M.H.; Yoon, Y.; Kim, J.; Hwang, S.G.; Han, Y.H.; Kim, J.S. miR-550a-3-5p acts as a tumor suppressor and reverses BRAF inhibitor resistance through the direct targeting of YAP. Cell Death Dis. 2018, 9, 640. [Google Scholar] [CrossRef] [PubMed]
- Diaz-Martinez, M.; Benito-Jardon, L.; Alonso, L.; Koetz-Ploch, L.; Hernando, E.; Teixido, J. miR-204-5p and miR-211-5p Contribute to BRAF Inhibitor Resistance in Melanoma. Cancer Res. 2018, 78, 1017–1030. [Google Scholar] [CrossRef] [Green Version]
- Fattore, L.; Ruggiero, C.F.; Pisanu, M.E.; Liguoro, D.; Cerri, A.; Costantini, S.; Capone, F.; Acunzo, M.; Romano, G.; Nigita, G.; et al. Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma. Cell Death Differ. 2019, 26, 1267–1282. [Google Scholar] [CrossRef] [Green Version]
- Vergani, E.; Dugo, M.; Cossa, M.; Frigerio, S.; Di Guardo, L.; Gallino, G.; Mattavelli, I.; Vergani, B.; Lalli, L.; Tamborini, E.; et al. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators. Cell Commun. Signal. 2020, 18, 156. [Google Scholar] [CrossRef] [PubMed]
- Gebhardt, C.; Sevko, A.; Jiang, H.H.; Lichtenberger, R.; Reith, M.; Tarnanidis, K.; Holland-Letz, T.; Umansky, L.; Beckhove, P.; Sucker, A.; et al. Myeloid Cells and Related Chronic Inflammatory Factors as Novel Predictive Markers in Melanoma Treatment with Ipilimumab. Clin. Cancer Res. 2015, 21, 5453–5459. [Google Scholar] [CrossRef] [Green Version]
- Walter, S.; Weinschenk, T.; Stenzl, A.; Zdrojowy, R.; Pluzanska, A.; Szczylik, C.; Staehler, M.; Brugger, W.; Dietrich, P.Y.; Mendrzyk, R.; et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat. Med. 2012, 18, 1254–1261. [Google Scholar] [CrossRef]
- Daveri, E.; Vergani, E.; Shahaj, E.; Bergamaschi, L.; La Magra, S.; Dosi, M.; Castelli, C.; Rodolfo, M.; Rivoltini, L.; Vallacchi, V.; et al. microRNAs Shape Myeloid Cell-Mediated Resistance to Cancer Immunotherapy. Front. Immunol. 2020, 11, 1214. [Google Scholar] [CrossRef]
- Marschner, D.; Falk, M.; Javorniczky, N.R.; Hanke-Muller, K.; Rawluk, J.; Schmitt-Graeff, A.; Simonetta, F.; Haring, E.; Dicks, S.; Ku, M.; et al. MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors. JCI Insight 2020, 5, e132334. [Google Scholar] [CrossRef] [Green Version]
- Clark, W.H., Jr.; From, L.; Bernardino, E.A.; Mihm, M.C. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res. 1969, 29, 705–727. [Google Scholar]
- Maibach, F.; Sadozai, H.; Jafari, S.M.S.; Hunger, R.E.; Schenk, M. Tumor-Infiltrating Lymphocytes and Their Prognostic Value in Cutaneous Melanoma. Front. Immunol. 2020, 11, 2015. [Google Scholar] [CrossRef] [PubMed]
- Mihm, M.C.; Mule, J.J. Reflections on the Histopathology of Tumor-Infiltrating Lymphocytes in Melanoma and the Host Immune Response. Cancer Immunol. Res. 2015, 3, 827–835. [Google Scholar] [CrossRef] [Green Version]
- Radvanyi, L.G.; Bernatchez, C.; Zhang, M.; Fox, P.S.; Miller, P.; Chacon, J.; Wu, R.; Lizee, G.; Mahoney, S.; Alvarado, G.; et al. Specific Lymphocyte Subsets Predict Response to Adoptive Cell Therapy Using Expanded Autologous Tumor-Infiltrating Lymphocytes in Metastatic Melanoma Patients. Clin. Cancer Res. 2012, 18, 6758–6770. [Google Scholar] [CrossRef]
- Galore-Haskel, G.; Greenberg, E.; Yahav, I.; Markovits, E.; Ortenberg, R.; Shapira-Fromer, R.; Itzhaki, O.; Schachter, J.; Besser, M.J.; Markel, G. microRNA expression patterns in tumor infiltrating lymphocytes are strongly associated with response to adoptive cell transfer therapy. Cancer Immunol. Immunother. 2021, 70, 1541–1555. [Google Scholar] [CrossRef] [PubMed]
- Du, X.; Poltorak, A.; Wei, Y.; Beutler, B. Three novel mammalian toll-like receptors: Gene structure, expression, and evolution. Eur. Cytokine Netw. 2000, 11, 362–371. [Google Scholar] [PubMed]
- Martinez-Campos, C.; Burguete-Garcia, A.I.; Madrid-Marina, V. Role of TLR9 in Oncogenic Virus-Produced Cancer. Viral. Immunol. 2017, 30, 98–105. [Google Scholar] [CrossRef] [PubMed]
- Tuomela, J.; Sandholm, J.; Karihtala, P.; Ilvesaro, J.; Vuopala, K.S.; Kauppila, J.H.; Kauppila, S.; Chen, D.Q.; Pressey, C.; Harkonen, P.; et al. Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer. Breast. Cancer Res. Treat. 2012, 135, 481–493. [Google Scholar] [CrossRef]
- Rohatgi, A.; Kirkwood, J.M. Beyond PD-1: The Next Frontier for Immunotherapy in Melanoma. Front. Oncol. 2021, 11, 640314. [Google Scholar] [CrossRef] [PubMed]
- Milhem, M.; Gonzales, R.; Medina, T.; Kirkwood, J.M.; Buchbinder, E.; Mehmi, I.; Niu, J.X.; Shaheen, M.; Weight, R.; Margolin, K.; et al. Intratumoral toll-like receptor 9 (TLR9) agonist, CMP-001, in combination with pembrolizumab can reverse resistance to PD-1 inhibition in a phase Ib trial in subjects with advanced melanoma. Cancer Res. 2018, 78, CT144. [Google Scholar] [CrossRef]
- Milhem, M.; Zakharia, Y.; Davar, D.; Buchbinder, E.; Medina, T.; Daud, A.; Ribas, A.; Niu, J.X.; Gibney, G.; Margolin, K.; et al. Durable Responses in Anti-Pd-1 Refractory Melanoma Following Intratumoral Injection of a Toll-Like Receptor 9 (Tlr9) Agonist, Cmp-001, in Combination with Pembrolizumab. J. Immunother. Cancer 2020, 8, A2–A3. [Google Scholar]
- Milhem, M.; Zakharia, Y.; Davar, D.; Buchbinder, E.; Medina, T.; Daud, A.; Ribas, A.; Niu, J.X.; Gibney, G.; Margolin, K.; et al. Intratumoral Injection of Cmp-001, a Toll-Like Receptor 9 (Tlr9) Agonist, in Combination with Pembrolizumab Reversed Programmed Death Receptor 1 (Pd-1) Blockade Resistance in Advanced Melanoma. J. Immunother. Cancer 2020, 8, A186–A187. [Google Scholar]
- Reilley, M.; Tsimberidou, A.M.; Piha-Paul, S.A.; Yap, T.A.; Fu, S.Q.; Naing, A.; Rodon, J.; Nguyen, L.M.; Ager, C.; Meng, M.; et al. Phase 1 trial of TLR9 agonist lefitolimod in combination with CTLA-4 checkpoint inhibitor ipilimumab in advanced tumors. J. Clin. Oncol. 2019, 37, TPS2669. [Google Scholar] [CrossRef]
- Karime, C.; Wang, J.; Woodhead, G.; Mody, K.; Hennemeyer, C.T.; Borad, M.J.; Mahadevan, D.; Chandana, S.R.; Babiker, H. Tilsotolimod: An investigational synthetic toll-like receptor 9 (TLR9) agonist for the treatment of refractory solid tumors and melanoma. Expert Opin. Investig. Drugs 2022, 31, 1–13. [Google Scholar] [CrossRef]
- Bomben, R.; Gobessi, S.; Dal Bo, M.; Volinia, S.; Marconi, D.; Tissino, E.; Benedetti, D.; Zucchetto, A.; Rossi, D.; Gaidano, G.; et al. The miR-17 approximately 92 family regulates the response to Toll-like receptor 9 triggering of CLL cells with unmutated IGHV genes. Leukemia 2012, 26, 1584–1593. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- He, Y.; Feng, D.; Li, M.; Gao, Y.; Ramirez, T.; Cao, H.; Kim, S.J.; Yang, Y.; Cai, Y.; Ju, C.; et al. Hepatic mitochondrial DNA/Toll-like receptor 9/MicroRNA-223 forms a negative feedback loop to limit neutrophil overactivation and acetaminophen hepatotoxicity in mice. Hepatology 2017, 66, 220–234. [Google Scholar] [CrossRef] [PubMed]
- Rogers, G.L.; Herzog, R.W. One MicroRNA Controls Both Angiogenesis and TLR-mediated Innate Immunity to Nucleic Acids. Mol. Ther. 2014, 22, 249–250. [Google Scholar] [CrossRef] [Green Version]
- Xu, L.; Wen, Z.K.; Zhou, Y.; Liu, Z.M.; Li, Q.C.; Fei, G.R.; Luo, J.M.; Ren, T. MicroRNA-7-regulated TLR9 signaling-enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/Akt pathway. Mol. Biol. Cell 2013, 24, 42–55. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.J.; Wang, C.H.; Zhou, Y.; Liao, Z.Y.; Zhu, S.F.; Hu, Y.; Chen, C.; Luo, J.M.; Wen, Z.K.; Xu, L. TLR9 signaling repressed tumor suppressor miR-7 expression through up-regulation of HuR in human lung cancer cells. Cancer Cell Int. 2013, 13, 90. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Joshi, P.; Kooshki, M.; Aldrich, W.; Varghai, D.; Zborowski, M.; Singh, A.D.; Triozzi, P.L. Expression of natural killer cell regulatory microRNA by uveal melanoma cancer stem cells. Clin. Exp. Metastas. 2016, 33, 829–838. [Google Scholar] [CrossRef]
- Achberger, S.; Aldrich, W.; Tubbs, R.; Crabb, J.W.; Singh, A.D.; Triozzi, P.L. Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease. Mol. Immunol. 2014, 58, 182–186. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Venza, I.; Visalli, M.; Beninati, C.; Benfatto, S.; Teti, D.; Venza, M. IL-10R alpha expression is post-transcriptionally regulated by miR-15a, miR-185, and miR-211 in melanoma. BMC. Med. Genom. 2015, 8, 81. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mastroianni, J.; Stickel, N.; Andrlova, H.; Hanke, K.; Melchinger, W.; Duquesne, S.; Schmidt, D.; Falk, M.; Andrieux, G.; Pfeifer, D.; et al. miR-146a Controls Immune Response in the Melanoma Microenvironment. Cancer Res. 2019, 79, 183–195. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hermeking, H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010, 17, 193–199. [Google Scholar] [CrossRef] [PubMed]
- Garofalo, M.; Jeon, Y.J.; Nuovo, G.J.; Middleton, J.; Secchiero, P.; Joshi, P.; Alder, H.; Nazaryan, N.; Di Leva, G.; Romano, G.; et al. Correction: MiR-34a/c-Dependent PDGFR-alpha/beta Downregulation Inhibits Tumorigenesis and Enhances TRAIL-Induced Apoptosis in Lung Cancer. PLoS ONE 2022, 17, e0267628. [Google Scholar] [CrossRef]
- Shin, J.; Xie, D.; Zhong, X.P. MicroRNA-34a enhances T cell activation by targeting diacylglycerol kinase zeta. PLoS ONE 2013, 8, e77983. [Google Scholar] [CrossRef]
- Cortez, M.A.; Ivan, C.; Valdecanas, D.; Wang, X.; Peltier, H.J.; Ye, Y.; Araujo, L.; Carbone, D.P.; Shilo, K.; Giri, D.K.; et al. PDL1 Regulation by p53 via miR-34. J. Natl. Cancer Inst. 2016, 108, djv303. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, X.; Li, J.G.; Dong, K.; Lin, F.; Long, M.; Ouyang, Y.R.; Wei, J.X.; Chen, X.; Weng, Y.Y.; He, T.; et al. Tumor suppressor miR-34a targets PD-L1 and functions as a potential immunotherapeutic target in acute myeloid leukemia. Cell Signal 2015, 27, 443–452. [Google Scholar] [CrossRef] [PubMed]
- Daige, C.L.; Wiggins, J.F.; Priddy, L.; Nelligan-Davis, T.; Zhao, J.; Brown, D. Systemic Delivery of a miR34a Mimic as a Potential Therapeutic for Liver Cancer. Mol. Cancer 2014, 13, 2352–2360. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hong, D.V.S.; Kang, Y.K.; Borad, M.; Sachdev, J.; Ejadi, S.; Lim, H.Y.; Brenner, A.J.; Park, K.; Lee, J.L.; Kim, T.Y.; et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br. J. Cancer 2020, 122, 1630–1637. [Google Scholar] [CrossRef] [PubMed]
- He, W.; Turkeshi, A.; Li, X.T.; Zhang, H.W. Progress in systemic co-delivery of microRNAs and chemotherapeutics for cancer treatment by using lipid-based nanoparticles. Ther. Deliv. 2020, 11, 591–603. [Google Scholar] [CrossRef]
- Yang, C.; Wang, R.; Hardy, P. Potential of miRNA-Based Nanotherapeutics for Uveal Melanoma. Cancers 2021, 13, 5192. [Google Scholar] [CrossRef] [PubMed]
- Selvam, A.K.; Jawad, R.; Gramignoli, R.; Achour, A.; Salter, H.; Bjornstedt, M. A Novel mRNA-Mediated and MicroRNA-Guided Approach to Specifically Eradicate Drug-Resistant Hepatocellular Carcinoma Cell Lines by Se-Methylselenocysteine. Antioxidants 2021, 10, 1094. [Google Scholar] [CrossRef] [PubMed]
- O’Neill, C.P.; Dwyer, R.M. Nanoparticle-Based Delivery of Tumor Suppressor microRNA for Cancer Therapy. Cells 2020, 9, 521. [Google Scholar] [CrossRef] [Green Version]
- Chen, Y.; Zhu, X.; Zhang, X.; Liu, B.; Huang, L. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol. Ther. 2010, 18, 1650–1656. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, Y.; Crawford, M.; Yu, B.; Mao, Y.; Nana-Sinkam, S.P.; Lee, L.J. MicroRNA delivery by cationic lipoplexes for lung cancer therapy. Mol. Pharm. 2011, 8, 1381–1389. [Google Scholar] [CrossRef] [PubMed]
- Yaghi, N.K.; Wei, J.; Hashimoto, Y.; Kong, L.Y.; Gabrusiewicz, K.; Nduom, E.K.; Ling, X.; Huang, N.; Zhou, S.; Kerrigan, B.C.; et al. Immune modulatory nanoparticle therapeutics for intracerebral glioma. Neuro. Oncol. 2017, 19, 372–382. [Google Scholar] [CrossRef] [Green Version]
- Shi, S.; Han, L.; Deng, L.; Zhang, Y.; Shen, H.; Gong, T.; Zhang, Z.; Sun, X. Dual drugs (microRNA-34a and paclitaxel)-loaded functional solid lipid nanoparticles for synergistic cancer cell suppression. J. Control. Release 2014, 194, 228–237. [Google Scholar] [CrossRef] [PubMed]
- Hanna, J.; Hossein, G.S.; Kocerha, J. The Potential for microRNA Therapeutics and Clinical Research. Front. Genet. 2019, 10, 478. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, T.; Nguyen, N.T.; Xie, Y.; Sun, X.; Li, Q.; Li, X. Inorganic Nanocrystals Functionalized Mesoporous Silica Nanoparticles: Fabrication and Enhanced Bio-applications. Front. Chem. 2017, 5, 118. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bharti, C.; Nagaich, U.; Pal, A.K.; Gulati, N. Mesoporous silica nanoparticles in target drug delivery system: A review. Int. J. Pharm. Investig. 2015, 5, 124–133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Della Rosa, G.; Di Corato, R.; Carpi, S.; Polini, B.; Taurino, A.; Tedeschi, L.; Nieri, P.; Rinaldi, R.; Aloisi, A. Tailoring of silica-based nanoporous pod by spermidine multi-activity. Sci. Rep. 2020, 10, 21142. [Google Scholar] [CrossRef] [PubMed]
- Yang, L.; Li, F.; Cao, Y.; Liu, Q.; Jing, G.; Niu, J.; Sun, F.; Qian, Y.; Wang, S.; Li, A. Multifunctional silica nanocomposites prime tumoricidal immunity for efficient cancer immunotherapy. J. Nanobiotechnol. 2021, 19, 328. [Google Scholar] [CrossRef] [PubMed]
- Chaudhari, R.; Nasra, S.; Meghani, N.; Kumar, A. MiR-206 conjugated gold nanoparticle based targeted therapy in breast cancer cells. Sci. Rep. 2022, 12, 4713. [Google Scholar] [CrossRef]
- Ferreira, D.; Fontinha, D.; Martins, C.; Pires, D.; Fernandes, A.R.; Baptista, P.V. Gold Nanoparticles for Vectorization of Nucleic Acids for Cancer Therapeutics. Molecules 2020, 25, 3489. [Google Scholar] [CrossRef] [PubMed]
- Milan Rois, P.; Latorre, A.; Rodriguez Diaz, C.; Del Moral, A.; Somoza, A. Reprogramming Cells for Synergistic Combination Therapy with Nanotherapeutics against Uveal Melanoma. Biomimetics 2018, 3, 28. [Google Scholar] [CrossRef] [PubMed]
- Szentirmai, V.; Wacha, A.; Nemeth, C.; Kitka, D.; Racz, A.; Heberger, K.; Mihaly, J.; Varga, Z. Reagent-free total protein quantification of intact extracellular vesicles by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Anal. Bioanal. Chem. 2020, 412, 4619–4628. [Google Scholar] [CrossRef]
- Bebelman, M.P.; Janssen, E.; Pegtel, D.M.; Crudden, C. The forces driving cancer extracellular vesicle secretion. Neoplasia 2021, 23, 149–157. [Google Scholar] [CrossRef] [PubMed]
- Luo, T.; von der Ohe, J.; Hass, R. MSC-Derived Extracellular Vesicles in Tumors and Therapy. Cancers 2021, 13, 5212. [Google Scholar] [CrossRef]
- Cheng, Y.C.; Chang, Y.A.; Chen, Y.J.; Sung, H.M.; Bogeski, I.; Su, H.L.; Hsu, Y.L.; Wang, H.D. The Roles of Extracellular Vesicles in Malignant Melanoma. Cells 2021, 10, 2740. [Google Scholar] [CrossRef] [PubMed]
- Zhan, Q.; Yi, K.; Qi, H.; Li, S.; Li, X.; Wang, Q.; Wang, Y.; Liu, C.; Qiu, M.; Yuan, X.; et al. Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy. Theranostics 2020, 10, 7889–7905. [Google Scholar] [CrossRef]
- Tarach, P.; Janaszewska, A. Recent Advances in Preclinical Research Using PAMAM Dendrimers for Cancer Gene Therapy. Int. J. Mol. Sci. 2021, 22, 2912. [Google Scholar] [CrossRef] [PubMed]
- Dzmitruk, V.; Apartsin, E.; Ihnatsyeu-Kachan, A.; Abashkin, V.; Shcharbin, D.; Bryszewska, M. Dendrimers Show Promise for siRNA and microRNA Therapeutics. Pharmaceutics 2018, 10, 126. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mekuria, S.L.; Li, J.; Song, C.; Gao, Y.; Ouyang, Z.J.; Shen, M.W.; Shi, X.Y. Facile Formation of PAMAM Dendrimer Nanoclusters for Enhanced Gene Delivery and Cancer Gene Therapy. ACS Appl. Bio Mater. 2021, 4, 7168–7175. [Google Scholar] [CrossRef] [PubMed]
- Delyanee, M.; Akbari, S.; Solouk, A. Amine-terminated dendritic polymers as promising nanoplatform for diagnostic and therapeutic agents’ modification: A review. Eur. J. Med. Chem. 2021, 221, 113572. [Google Scholar] [CrossRef] [PubMed]
- Maghsoudnia, N.; Eftekhari, R.B.; Sohi, A.N.; Dorkoosh, F.A. Chloroquine Assisted Delivery of microRNA Mimic Let-7b to NSCLC Cell Line by PAMAM (G5)—HA Nano-Carrier. Curr. Drug. Deliv. 2021, 18, 31–43. [Google Scholar] [CrossRef] [PubMed]
- Maghsoudni, N.; Eftekhari, R.B.; Sohi, A.N.; Norouzi, P.; Akbari, H.; Ghahremani, M.H.; Soleimani, M.; Amini, M.; Samadi, F.; Dorkoosh, F.A. Mitochondrial delivery of microRNA mimic let-7b to NSCLC cells by PAMAM-based nanoparticles. J. Drug Target. 2020, 28, 818–830. [Google Scholar] [CrossRef]
- Cassano, R.; Cuconato, M.; Calviello, G.; Serini, S.; Trombino, S. Recent Advances in Nanotechnology for the Treatment of Melanoma. Molecules 2021, 26, 785. [Google Scholar] [CrossRef]
- Patra, J.K.; Das, G.; Fraceto, L.F.; Campos, E.V.R.; Rodriguez-Torres, M.D.P.; Acosta-Torres, L.S.; Diaz-Torres, L.A.; Grillo, R.; Swamy, M.K.; Sharma, S.; et al. Nano based drug delivery systems: Recent developments and future prospects. J. Nanobiotechnol. 2018, 16, 71. [Google Scholar] [CrossRef] [Green Version]
- Yu, H.; Ning, N.; Meng, X.; Chittasupho, C.; Jiang, L.; Zhao, Y. Sequential Drug Delivery in Targeted Cancer Therapy. Pharmaceutics 2022, 14, 573. [Google Scholar] [CrossRef]
- Stremersch, S.; Vandenbroucke, R.E.; Van Wonterghem, E.; Hendrix, A.; De Smedt, S.C.; Raemdonck, K. Comparing exosome-like vesicles with liposomes for the functional cellular delivery of small RNAs. J. Control. Release 2016, 232, 51–61. [Google Scholar] [CrossRef]
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Dong, L.; Tian, X.; Zhao, Y.; Tu, H.; Wong, A.; Yang, Y. The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy. Int. J. Mol. Sci. 2022, 23, 14775. https://doi.org/10.3390/ijms232314775
Dong L, Tian X, Zhao Y, Tu H, Wong A, Yang Y. The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy. International Journal of Molecular Sciences. 2022; 23(23):14775. https://doi.org/10.3390/ijms232314775
Chicago/Turabian StyleDong, Linyinxue, Xuechen Tian, Yunqi Zhao, Haohong Tu, Aloysius Wong, and Yixin Yang. 2022. "The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy" International Journal of Molecular Sciences 23, no. 23: 14775. https://doi.org/10.3390/ijms232314775