Skip to main content

Immunotherapy for Difficult-to-Treat Invasive Fungal Diseases

  • Chapter
  • First Online:
Principles and Practice of Cancer Infectious Diseases

Part of the book series: Current Clinical Oncology ((CCO))

  • 1436 Accesses

Abstract

Opportunistic fungal diseases occur most ­commonly in highly immunocompromised patients, such as those with prolonged neutropenia or transplant recipients treated with ­intensive immunosuppression. Significant advances have been made in antifungal agents, which have led to improved therapeutic outcomes as well as a greater emphasis on antifungal prophylaxis targeted to the highly immunocompromised. In addition, we are gaining more knowledge about how our immune system recognizes fungi and protects us from fungal disease, while limiting potentially injurious inflammation and allergy. This knowledge has led to novel experimental approaches for immunotherapy. Progress in paving the way from promising preclinical approaches and limited clinical experience to properly conducted clinical trials has been poor – a reflection of invasive fungal diseases being relatively uncommon and the heterogeneity of the patient populations at risk, and insufficient funding for multicenter clinical immunotherapeutic trials. We describe our approaches to immunotherapy for severe and refractory invasive fungal diseases, realizing that important gaps in knowledge exist regarding benefit and toxicity. Future perspectives on immunotherapy are discussed.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 259.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Institutional subscriptions

Similar content being viewed by others

References

  1. Blumberg HM, Jarvis WR, Soucie JM, et al. Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey. Clin Infect Dis. 2001;33:177–86.

    Article  PubMed  CAS  Google Scholar 

  2. Bow EJ, Loewen R, Cheang MS, Shore TB, Rubinger M, Schacter B. Cytotoxic therapy-induced D-xylose malabsorption and invasive infection during remission-induction therapy for acute myeloid leukemia in adults. J Clin Oncol. 1997;15:2254–61.

    PubMed  CAS  Google Scholar 

  3. Galgiani JN, Ampel NM, Blair JE, et al. IDSA guidelines: coccidioidomycosis. Clin Infect Dis. 2005;41:1217–23.

    Article  PubMed  Google Scholar 

  4. Louie L, Ng S, Hajjeh R, et al. Influence of host genetics on the severity of coccidioidomycosis. Emerg Infect Dis. 1999;5:672–80.

    Article  PubMed  CAS  Google Scholar 

  5. Segal BH. Aspergillosis. N Engl J Med. 2009;360:1870–84.

    Article  PubMed  CAS  Google Scholar 

  6. Gerson SL, Talbot GH, Hurwitz S, Strom BL, Lusk EJ, Cassileth PA. Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Intern Med. 1984;100:345–51.

    Article  PubMed  CAS  Google Scholar 

  7. Weinberger M, Elattar I, Marshall D, et al. Patterns of infection in patients with aplastic anemia and the emergence of Aspergillus as a major cause of death. Medicine (Baltimore). 1992;71:24–43.

    CAS  Google Scholar 

  8. Marty FM, Rubin RH. The prevention of infection post-transplant: the role of prophylaxis, preemptive and empiric therapy. Transpl Int. 2006;19:2–11.

    Article  PubMed  Google Scholar 

  9. Wald A, Leisenring W, van Burik JA, Bowden RA. Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation. J Infect Dis. 1997;175:1459–66.

    Article  PubMed  CAS  Google Scholar 

  10. Baddley JW, Stroud TP, Salzman D, Pappas PG. Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis. 2001;32:1319–24.

    Article  PubMed  CAS  Google Scholar 

  11. Grow WB, Moreb JS, Roque D, et al. Late onset of invasive aspergillus infection in bone marrow transplant patients at a university hospital. Bone Marrow Transplant. 2002;29:15–9.

    Article  PubMed  CAS  Google Scholar 

  12. Jantunen E, Ruutu P, Niskanen L, et al. Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients. Bone Marrow Transplant. 1997;19:801–8.

    Article  PubMed  CAS  Google Scholar 

  13. McWhinney PH, Kibbler CC, Hamon MD, et al. Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years’ experience. Clin Infect Dis. 1993;17:397–404.

    Article  PubMed  CAS  Google Scholar 

  14. Yuen KY, Woo PC, Ip MS, et al. Stage-specific manifestation of mold infections in bone marrow transplant recipients: risk factors and clinical significance of positive concentrated smears. Clin Infect Dis. 1997;25:37–42.

    Article  PubMed  CAS  Google Scholar 

  15. Marr KA, Carter RA, Boeckh M, Martin P, Corey L. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood. 2002;100:4358–66.

    Article  PubMed  CAS  Google Scholar 

  16. Shaukat A, Bakri F, Young P, et al. Invasive filamentous fungal infections in allogeneic hematopoietic stem cell transplant recipients after recovery from neutropenia: clinical, radiologic, and pathologic characteristics. Mycopathologia. 2005;159:181–8.

    Article  PubMed  Google Scholar 

  17. van Burik JA, Carter SL, Freifeld AG, et al. Higher risk of cytomegalovirus and aspergillus infections in recipients of T cell-depleted unrelated bone marrow: analysis of infectious complications in patients treated with T cell depletion versus immunosuppressive therapy to prevent graft-versus-host disease. Biol Blood Marrow Transplant. 2007;13:1487–98.

    Article  PubMed  Google Scholar 

  18. Morgan J, Wannemuehler KA, Marr KA, et al. Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med Mycol. 2005;43 Suppl 1:S49–58.

    Article  PubMed  Google Scholar 

  19. Hadjiliadis D, Sporn TA, Perfect JR, Tapson VF, Davis RD, Palmer SM. Outcome of lung transplantation in patients with mycetomas. Chest. 2002;121:128–34.

    Article  PubMed  Google Scholar 

  20. Winkelstein JA, Marino MC, Johnston RBJr, et al. Chronic granulomatous disease: report on a national registry of 368 patients. Medicine (Baltimore). 2000;79:155–69.

    Article  CAS  Google Scholar 

  21. Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000;79:170–200.

    Article  CAS  Google Scholar 

  22. Rowe JM. Concurrent use of growth factors and chemotherapy in acute leukemia. Curr Opin Hematol. 2000;7:197–202.

    Article  PubMed  CAS  Google Scholar 

  23. Ozer H, Armitage JO, Bennett CL, et al. 2000 update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. American Society of Clinical Oncology Growth Factors Expert Panel. J Clin Oncol. 2000;18:3558–85.

    PubMed  CAS  Google Scholar 

  24. Godwin JE, Kopecky KJ, Head DR, et al. A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study (9031). Blood. 1998;91:3607–15.

    PubMed  CAS  Google Scholar 

  25. Heil G, Hoelzer D, Sanz MA, et al. A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group. Blood. 1997;90:4710–8.

    PubMed  CAS  Google Scholar 

  26. Giles FJ. Monocyte-macrophages, granulocyte-macrophage ­colony-stimulating factor, and prolonged survival among patients with acute myeloid leukemia and stem cell transplants. Clin Infect Dis. 1998;26:1282–9.

    Article  PubMed  CAS  Google Scholar 

  27. Rowe JM, Andersen JW, Mazza JJ, et al. A randomized placebo-controlled phase III study of granulocyte- macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995;86:457–62.

    PubMed  CAS  Google Scholar 

  28. Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24:3187–205.

    Article  PubMed  CAS  Google Scholar 

  29. Lyman GH, Kleiner JM. Summary and comparison of myeloid growth factor guidelines in patients receiving cancer chemotherapy. J Natl Compr Canc Netw. 2007;5:217–28.

    PubMed  CAS  Google Scholar 

  30. Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative ­relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64:328–40.

    Article  PubMed  CAS  Google Scholar 

  31. Vora S, Purimetla N, Brummer E, Stevens DA. Activity of voriconazole, a new triazole, combined with neutrophils or monocytes against Candida albicans: effect of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor ­[published erratum appears in Antimicrob Agents Chemother 1998 Aug;42(8):2152]. Antimicrob Agents Chemother. 1998;42:907–10.

    PubMed  CAS  Google Scholar 

  32. Sionov E, Mendlovic S, Segal E. Experimental systemic murine aspergillosis: treatment with polyene and caspofungin combination and G-CSF. J Antimicrob Chemother. 2005;56:594–7.

    Article  PubMed  CAS  Google Scholar 

  33. Sionov E, Segal E. Polyene and cytokine treatment of experimental aspergillosis. FEMS Immunol Med Microbiol. 2003;39:221–7.

    Article  PubMed  CAS  Google Scholar 

  34. Kullberg BJ, Vandewoude K, Herbrecht R, Jacobs F, Aoun M, Kujath P. A double-blind, randomized, placebo-controlled phase II study of filgrastim (recombinant granulocyte colony-stimulating factor) in combination with fluconazole for treatment of invasive candidiasis and candidemia in nonneutropenic patients. In: 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego, CA; 1998. p. J-100.

    Google Scholar 

  35. Nemunaitis J. Use of macrophage colony-stimulating factor in the treatment of fungal infections. Clin Infect Dis. 1998;26:1279–81.

    Article  PubMed  CAS  Google Scholar 

  36. Sloand EM, Kim S, Maciejewski JP, et al. Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo. Blood. 2000;95:2269–74.

    PubMed  CAS  Google Scholar 

  37. Rutella S, Pierelli L, Bonanno G, et al. Role for granulocyte ­colony-stimulating factor in the generation of human T regulatory type 1 cells. Blood. 2002;100:2562–71.

    Article  PubMed  CAS  Google Scholar 

  38. Volpi I, Perruccio K, Tosti A, et al. Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-­mismatched hematopoietic transplants. Blood. 2001;97:2514–21.

    Article  PubMed  CAS  Google Scholar 

  39. Choi JH, Brummer E, Kang YJ, Jones PP, Stevens DA. Inhibitor kappaB and nuclear factor kappaB in granulocyte-macrophage colony-stimulating factor antagonism of dexamethasone suppression of the macrophage response to Aspergillus fumigatus conidia. J Infect Dis. 2006;193:1023–8.

    Article  PubMed  CAS  Google Scholar 

  40. Groll A, Renz S, Gerein V, et al. Fatal haemoptysis associated with invasive pulmonary aspergillosis treated with high-dose amphotericin B and granulocyte-macrophage colony-stimulating factor (GM-CSF). Mycoses. 1992;35:67–75.

    Article  PubMed  CAS  Google Scholar 

  41. Safdar A, Rodriguez G, Rolston KV, et al. High-dose caspofungin combination antifungal therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007;39:157–64.

    Article  PubMed  CAS  Google Scholar 

  42. Bensinger WI, Price TH, Dale DC, et al. The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis [see comments]. Blood. 1993;81:1883–8.

    PubMed  CAS  Google Scholar 

  43. Dale DC, Liles WC, Llewellyn C, Rodger E, Price TH. Neutrophil transfusions: kinetics and functions of neutrophils mobilized with granulocyte-colony-stimulating factor and dexamethasone [see comments]. Transfusion. 1998;38:713–21.

    Article  PubMed  CAS  Google Scholar 

  44. Price TH, Bowden RA, Boeckh M, et al. Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoeitic stem cell transplantation. Blood. 2000;95:3302–9.

    PubMed  CAS  Google Scholar 

  45. Wright DG, Robichaud KJ, Pizzo PA, Deisseroth AB. Lethal pulmonary reactions associated with the combined use of amphotericin B and leukocyte transfusions. N Engl J Med. 1981;304:1185–9.

    Article  PubMed  CAS  Google Scholar 

  46. Stroncek DF, Leonard K, Eiber G, Malech HL, Gallin JI, Leitman SF. Alloimmunization after granulocyte transfusions. Transfusion. 1996;36:1009–15.

    Article  PubMed  CAS  Google Scholar 

  47. Nichols WG, Price T, Boeckh M. Cytomegalovirus infections in cancer patients receiving granulocyte transfusions. Blood. 2002;99: 3483–4.

    Article  PubMed  CAS  Google Scholar 

  48. Schalm SW, Weiland O, Hansen BE, et al. Interferon-ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trials. Eurohep Study Group for Viral Hepatitis. Gastroenterology. 1999;117:408–13.

    Article  PubMed  CAS  Google Scholar 

  49. Stevens DA. Combination immunotherapy and antifungal chemotherapy. Clin Infect Dis. 1998;26:1266–9.

    Article  PubMed  CAS  Google Scholar 

  50. Segal BH, Kwon-Chung J, Walsh TJ, et al. Immunotherapy for fungal infections. Clin Infect Dis. 2006;42:507–15.

    Article  PubMed  CAS  Google Scholar 

  51. Segal BH, Holland SM. Interferon-gamma in infectious diseases. In: Kawakami K, Stevens DA, editors. Immunomodulators as promising therapeutic agents against infectious diseases. Kerala, India: Research Signpost; 2004. p. 23–54.

    Google Scholar 

  52. Stevens DA, Brummer E, Clemons KV. Interferon-gamma as an antifungal. J Infect Dis. 2006;194 Suppl 1:S33–7.

    Article  PubMed  CAS  Google Scholar 

  53. Wang J, Wakeham J, Harkness R, Xing Z. Macrophages are a significant source of type 1 cytokines during mycobacterial infection. J Clin Invest. 1999;103:1023–9.

    Article  PubMed  CAS  Google Scholar 

  54. Mountford AP, Coulson PS, Cheever AW, Sher A, Wilson RA, Wynn TA. Interleukin-12 can directly induce T-helper 1 responses in interferon-gamma (IFN-gamma) receptor-deficient mice, but requires IFN-gamma signalling to downregulate T-helper 2 responses. Immunology. 1999;97:588–94.

    Article  PubMed  CAS  Google Scholar 

  55. Tomura M, Maruo S, Mu J, et al. Differential capacities of CD4+, CD8+, and CD4-CD8- T cell subsets to express IL-18 receptor and produce IFN-gamma in response to IL-18. J Immunol. 1998;160:3759–65.

    PubMed  CAS  Google Scholar 

  56. Boehm U, Klamp T, Groot M, Howard JC. Cellular responses to interferon-gamma. Annu Rev Immunol. 1997;15:749–95.

    Article  PubMed  CAS  Google Scholar 

  57. Pien GC, Satoskar AR, Takeda K, Akira S, Biron CA. Cutting edge: selective IL-18 requirements for induction of compartmental IFN-gamma responses during viral infection. J Immunol. 2000;165:4787–91.

    PubMed  CAS  Google Scholar 

  58. The International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med. 1991;324:509–16.

    Article  Google Scholar 

  59. Pappas PG, Bustamante B, Ticona E, et al. Recombinant interferon-gamma 1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis. J Infect Dis. 2004;189:2185–91.

    Article  PubMed  CAS  Google Scholar 

  60. Nagai H, Guo J, Choi H, Kurup V. Interferon-gamma and tumor necrosis factor-alpha protect mice from invasive aspergillosis. J Infect Dis. 1995;172:1554–60.

    Article  PubMed  CAS  Google Scholar 

  61. Stevens DA. Th1/Th2 in aspergillosis. Med Mycol. 2006;44:S229–35.

    Article  CAS  Google Scholar 

  62. Roilides E, Uhlig K, Venzon D, Pizzo PA, Walsh TJ. Enhancement of oxidative response and damage caused by human neutrophils to Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon. Infect Immun. 1993;61:1185–93.

    PubMed  CAS  Google Scholar 

  63. Roilides E, Uhlig K, Venzon D, Pizzo PA, Walsh TJ. Prevention of corticosteroid-induced suppression of human polymorphonuclear leukocyte-induced damage of Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon. Infect Immun. 1993;61:4870–7.

    PubMed  CAS  Google Scholar 

  64. Roilides E, Holmes A, Blake C, Venzon D, Pizzo PA, Walsh TJ. Antifungal activity of elutriated human monocytes against Aspergillus fumigatus hyphae: enhancement by granulocyte-macrophage colony-stimulating factor and interferon-gamma. J Infect Dis. 1994;170:894–9.

    Article  PubMed  CAS  Google Scholar 

  65. Rex JH, Bennett JE, Gallin JI, Malech HL, DeCarlo ES, Melnick DA. In vivo interferon-gamma therapy augments the in vitro ability of chronic granulomatous disease neutrophils to damage Aspergillus hyphae. J Infect Dis. 1991;163:849–52.

    Article  PubMed  CAS  Google Scholar 

  66. Dignani MC, Rex JH, Chan KW, et al. Immunomodulation with interferon-gamma and colony stimulating factors for refractory fungal infections in patients with leukemia. Cancer. 2005;104:199–204.

    Article  PubMed  CAS  Google Scholar 

  67. Safdar A, Rodriguez G, Ohmagari N, et al. The safety of ­interferon-gamma-1b for invasive fungal infections after hematopoietic stem cell transplantation. Cancer. 2005;103:731–9.

    Article  PubMed  CAS  Google Scholar 

  68. Safdar A, Rodriguez GH, Lichtiger B, et al. Recombinant interferon gamma1b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions. Cancer. 2006;106:2664–71.

    Article  PubMed  CAS  Google Scholar 

  69. Brown GD. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol. 2006;6:33–43.

    Article  PubMed  CAS  Google Scholar 

  70. Romani L. Immunity to fungal infections. Nat Rev Immunol. 2004;4:1–23.

    Article  PubMed  CAS  Google Scholar 

  71. Netea MG, Van der Graaf C, Van der Meer JW, Kullberg BJ. Recognition of fungal pathogens by Toll-like receptors. Eur J Clin Microbiol Infect Dis. 2004;23:672–6.

    Article  PubMed  CAS  Google Scholar 

  72. Bellocchio S, Moretti S, Perruccio K, et al. TLRs govern neutrophil activity in aspergillosis. J Immunol. 2004;173:7406–15.

    PubMed  CAS  Google Scholar 

  73. Bellocchio S, Montagnoli C, Bozza S, et al. The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J Immunol. 2004;172:3059–69.

    PubMed  CAS  Google Scholar 

  74. Romani L, Montagnoli C, Bozza S, et al. The exploitation of distinct recognition receptors in dendritic cells determines the full range of host immune relationships with Candida albicans. Int Immunol. 2004;16:149–61.

    Article  PubMed  CAS  Google Scholar 

  75. Arning M, Kliche KO, Heer-Sonderhoff AH, Wehmeier A. Infusion-related toxicity of three different amphotericin B formulations and its relation to cytokine plasma levels. Mycoses. 1995;38:459–65.

    Article  PubMed  CAS  Google Scholar 

  76. Rogers PD, Kramer RE, Chapman SW, Cleary JD. Amphotericin B-induced interleukin-1beta expression in human monocytic cells is calcium and calmodulin dependent. J Infect Dis. 1999;180:1259–66.

    Article  PubMed  CAS  Google Scholar 

  77. Bellocchio S, Gaziano R, Bozza S, et al. Liposomal amphotericin B activates antifungal resistance with reduced toxicity by diverting Toll-like receptor signalling from TLR-2 to TLR-4. J Antimicrob Chemother. 2005;55:214–22.

    Article  PubMed  CAS  Google Scholar 

  78. Lewis RE, Chamilos G, Prince RA, Kontoyiannis DP. Pretreatment with empty liposomes attenuates the immunopathology of invasive pulmonary aspergillosis in corticosteroid-immunosuppressed mice. Antimicrob Agents Chemother. 2007;51:1078–81.

    Article  PubMed  CAS  Google Scholar 

  79. Petraitis V, Petraitiene R, Groll AH, et al. Antifungal efficacy, safety, and single-dose pharmacokinetics of LY303366, a novel echinocandin B, in experimental pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother. 1998;42:2898–905.

    PubMed  CAS  Google Scholar 

  80. Dennis CG, Greco WR, Brun Y, et al. Effect of amphotericin B and micafungin combination on survival, histopathology, and fungal burden in experimental aspergillosis in the p47phox-/- mouse model of chronic granulomatous disease. Antimicrob Agents Chemother. 2006;50:422–7.

    Article  PubMed  CAS  Google Scholar 

  81. Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med. 2003;197:1107–17.

    Article  PubMed  CAS  Google Scholar 

  82. Gersuk GM, Underhill DM, Zhu L, Marr KA. Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states. J Immunol. 2006;176:3717–24.

    PubMed  CAS  Google Scholar 

  83. Netea MG, Gow NA, Munro CA, et al. Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J Clin Invest. 2006;116(6):1642–50.

    Article  PubMed  CAS  Google Scholar 

  84. Hohl TM, Van Epps HL, Rivera A, et al. Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display. PLoS Pathog. 2005;1:e30.

    Article  PubMed  CAS  Google Scholar 

  85. Graham LM, Tsoni SV, Willment JA, et al. Soluble Dectin-1 as a tool to detect beta-glucans. J Immunol Methods. 2006;314:164–9.

    Article  PubMed  CAS  Google Scholar 

  86. Hohl TM, Feldmesser M, Perlin DS, Pamer EG. Caspofungin modulates inflammatory responses to Aspergillus fumigatus through stage-specific effects on fungal beta-glucan exposure. J Infect Dis. 2008;198:176–85.

    Article  PubMed  CAS  Google Scholar 

  87. Lamaris GA, Lewis RE, Chamilos G, et al. Caspofungin-mediated beta-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae. J Infect Dis. 2008;198:186–92.

    Article  PubMed  CAS  Google Scholar 

  88. Wheeler RT, Fink GR. A drug-sensitive genetic network masks fungi from the immune system. PLoS Pathog. 2006;2:e35.

    Article  PubMed  CAS  Google Scholar 

  89. Popolo L, Gilardelli D, Bonfante P, Vai M. Increase in chitin as an essential response to defects in assembly of cell wall polymers in the ggp1delta mutant of Saccharomyces cerevisiae. J Bacteriol. 1997;179:463–9.

    PubMed  CAS  Google Scholar 

  90. Spellberg BJ, Ibrahim AS, Avenissian V, et al. The anti-Candida albicans vaccine composed of the recombinant N terminus of Als1p reduces fungal burden and improves survival in both immunocompetent and immunocompromised mice. Infect Immun. 2005;73:6191–3.

    Article  PubMed  CAS  Google Scholar 

  91. Torosantucci A, Bromuro C, Chiani P, et al. A novel glyco-conjugate vaccine against fungal pathogens. J Exp Med. 2005;202:597–606.

    Article  PubMed  CAS  Google Scholar 

  92. Bozza S, Montagnoli C, Gaziano R, et al. Dendritic cell-based vaccination against opportunistic fungi. Vaccine. 2004;22:857–64.

    Article  PubMed  CAS  Google Scholar 

  93. Stevens DA. Vaccinate against aspergillosis! A call to arms of the immune system. Clin Infect Dis. 2004;38:1131–6.

    Article  PubMed  Google Scholar 

  94. Cox RA, Magee DM. Coccidioidomycosis: host response and ­vaccine development. Clin Microbiol Rev. 2004;17:804–39. table of contents.

    Article  PubMed  CAS  Google Scholar 

  95. Brummer E, Antonysamy MA, Bythadka L, Gullikson GW, Stevens DA. Effect of 3M-003, an imidazoquinoline analog of imiquimod, on phagocyte candidacidal activity directly and via peripheral blood mononuclear cell cytokines. FEMS Immunol Med Microbiol. 2010;59(1):81–9.

    Article  PubMed  CAS  Google Scholar 

  96. Brummer E, Stevens DA. Collectins and fungal pathogens: roles of surfactant proteins and mannose binding lectin in host resistance. Med Mycol. 2010;48(1):16–28.

    Article  PubMed  CAS  Google Scholar 

  97. Clemons KV, Kamberi P, Chiller TM, et al. Effects of interferon-gamma gene therapy in the murine central nervous system and concentrations in cerebrospinal fluid after intrathecal or intracerebral administration. Biotechnology 2005;4:11–18.

    Article  PubMed  CAS  Google Scholar 

  98. Kullberg BJ, Oude Lashof AM, Netea MG. Design of efficacy trials of cytokines in combination with antifungal drugs. Clin Infect Dis. 2004;39 Suppl 4:S218–23.

    Article  PubMed  Google Scholar 

  99. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327–60.

    Article  PubMed  CAS  Google Scholar 

  100. Segal BH, Freifeld AG, Baden LR, et al. Prevention and treatment of cancer-related infections. J Natl Compr Canc Netw. 2008;6:122–74.

    PubMed  Google Scholar 

  101. Singh N, Perfect JR. Immune reconstitution syndrome associated with opportunistic mycoses. Lancet Infect Dis. 2007;7:395–401.

    Article  PubMed  Google Scholar 

  102. Buescher ES, Gallin JI. Leukocyte transfusions in chronic granulomatous disease: persistence of transfused leukocytes in sputum. N Engl J Med. 1982;307:800–3.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Brahm H. Segal .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Segal, B.H., Safdar, A., Stevens, D.A. (2011). Immunotherapy for Difficult-to-Treat Invasive Fungal Diseases. In: Safdar, A. (eds) Principles and Practice of Cancer Infectious Diseases. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-644-3_29

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-644-3_29

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-643-6

  • Online ISBN: 978-1-60761-644-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics