Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Prognostic Biomarkers for Melanoma Immunotherapy

Abstract

Purpose of Review

Recent developments in immunotherapy have transformed the landscape of melanoma therapy. Here, we review markers for response to immunotherapy.

Recent Findings

Current immunotherapies disable immune checkpoints on T cells and other immune cells and allow immune rejection of tumor. This process depends crucially on a preexisting response to the development of the melanoma. Here we describe the complexity of the anti-tumor immune response and the links to the development of markers that are currently used or under investigation in the clinic.

Summary

We describe immune response biomarkers along with new developments that could translate into advances.

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

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.

    Holderfield M, Deuker MM, McCormick F, McMahon M. Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nat Rev Cancer. 2014 Jul;14(7):455–67.

  2. 2.

    Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010 Sep 30;467(7315):596–9.

  3. 3.

    Robert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med. 2019;381(7):626–36.

  4. 4.

    Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107–14.

  5. 5.

    Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–5.

  6. 6.

    Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.

  7. 7.

    Miller AJ, Mihm MC. Melanoma. N Engl J Med. 2006;355(1):51–65.

  8. 8.

    Shain AH, Joseph NM, Yu R, Benhamida J, Liu S, Prow T, et al. Genomic and transcriptomic analysis reveals incremental disruption of key signaling pathways during melanoma evolution. Cancer Cell. 2018;34(1):45–55 e4.

  9. 9.

    Shain AH, Bastian BC. From melanocytes to melanomas. Nat Rev Cancer. 2016;16(6):345–58.

  10. 10.

    Angelova M, Mlecnik B, Vasaturo A, Bindea G, Fredriksen T, Lafontaine L, et al. Evolution of metastases in space and time under immune selection. Cell. 2018;175(3):751–65 e16.

  11. 11.

    Boddupalli CS, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, et al. Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells. JCI Insight. 2016;1(21):e88955.

  12. 12.

    Lehmann B, Biburger M, Brückner C, Ipsen-Escobedo A, Gordan S, Lehmann C, et al. Tumor location determines tissue-specific recruitment of tumor-associated macrophages and antibody-dependent immunotherapy response. Sci Immunol. 2017;6:2(7).

  13. 13.

    Roh W, Chen P-L, Reuben A, Spencer CN, Prieto PA, Miller JP, et al. Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Sci Transl Med. 2017;01:9(379).

  14. 14.

    Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74.

  15. 15.

    Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014;515(7528):577–81.

  16. 16.

    Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137–48.

  17. 17.

    O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019;16(3):151–67.

  18. 18.

    Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, et al. PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors. J Clin Invest. 2014;124(5):2246–59.

  19. 19.

    Li H, van der Leun AM, Yofe I, Lubling Y, Gelbard-Solodkin D, van Akkooi ACJ, et al. Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma. Cell. 2019;176(4):775–89 e18.

  20. 20.

    Sade-Feldman M, Yizhak K, Bjorgaard SL, Ray JP, de Boer CG, Jenkins RW, et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell. 2019;176(1–2):404.

  21. 21.

    Vodnala SK, Eil R, Kishton RJ, Sukumar M, Yamamoto TN, Ha N-H, et al. T cell stemness and dysfunction in tumors are triggered by a common mechanism. Science. 2019;363(6434).

  22. 22.

    Anderson AC, Lord GM, Dardalhon V, Lee DH, Sabatos-Peyton CA, Glimcher LH, et al. T-bet, a Th1 transcription factor regulates the expression of Tim-3. Eur J Immunol. 2010;40(3):859–66.

  23. 23.

    Liu X, Wang Y, Lu H, Li J, Yan X, Xiao M, et al. Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction. Nature. 2019;567(7749):525–9.

  24. 24.

    Chen J, López-Moyado IF, Seo H, Lio C-WJ, Hempleman LJ, Sekiya T, et al. NR4A transcription factors limit CAR T cell function in solid tumours. Nature. 2019;567(7749):530–4.

  25. 25.

    • Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, Khan O, et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science. 2016;354(6316):1160–5 Establishes the concepts and findings relating to “exhausted” T cells.

  26. 26.

    Bengsch B, Johnson AL, Kurachi M, Odorizzi PM, Pauken KE, Attanasio J, et al. Bioenergetic insufficiencies due to metabolic alterations regulated by the inhibitory receptor PD-1 are an early driver of CD8(+) T cell exhaustion. Immunity. 2016;45(2):358–73.

  27. 27.

    • Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, et al. Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest. 2016;126(9):3447–52 Describes the connection between “exhausted” T cells and PD-1 response in melanoma.

  28. 28.

    Loo K, Tsai KK, Mahuron K, Liu J, Pauli ML, Sandoval PM, et al. Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy. JCI Insight [Internet]. 2017;2(14) Available from: https://insight.jci.org/articles/view/93433.

  29. 29.

    • Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017;545(7652):60–5 Points to reinvigoration of exhausted T cells in melanoma.

  30. 30.

    Im SJ, Hashimoto M, Gerner MY, Lee J, Kissick HT, Burger MC, et al. Defining CD8(+) T cells that provide the proliferative burst after PD-1 therapy. Nature. 2016;537(7620):417–21.

  31. 31.

    Kurtulus S, Madi A, Escobar G, Klapholz M, Nyman J, Christian E, et al. Checkpoint blockade immunotherapy induces dynamic changes in PD-1-CD8+ tumor-infiltrating T cells. Immunity. 2019;50(1):181–94 e6.

  32. 32.

    Siddiqui I, Schaeuble K, Chennupati V, Fuertes Marraco SA, Calderon-Copete S, Pais Ferreira D, et al. Intratumoral Tcf1+PD-1+CD8+ T cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy. Immunity. 2019;50(1):195–211 e10.

  33. 33.

    Danilo M, Chennupati V, Silva JG, Siegert S, Held W. Suppression of Tcf1 by inflammatory cytokines facilitates effector CD8 T cell differentiation. Cell Rep. 2018;22(8):2107–17.

  34. 34.

    Hsu J, Hodgins JJ, Marathe M, Nicolai CJ, Bourgeois-Daigneault M-C, Trevino TN, et al. Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. J Clin Invest. 2018;128(10):4654–68.

  35. 35.

    Barry KC, Hsu J, Broz ML, Cueto FJ, Binnewies M, Combes AJ, et al. A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments. Nat Med. 2018;24(8):1178–91.

  36. 36.

    Garris CS, Arlauckas SP, Kohler RH, Trefny MP, Garren S, Piot C, et al. Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12. Immunity. 2018;49(6):1148–61 e7.

  37. 37.

    Chow MT, Ozga AJ, Servis RL, Frederick DT, Lo JA, Fisher DE, et al. Intratumoral activity of the CXCR3 chemokine system is required for the efficacy of anti-PD-1 therapy. Immunity. 2019;50(6):1498–512 e5.

  38. 38.

    Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature. 2015;523(7559):231–5.

  39. 39.

    Spranger S, Gajewski TF. Tumor-intrinsic oncogene pathways mediating immune avoidance. Oncoimmunology. 2016 Mar;5(3):e1086862.

  40. 40.

    Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545(7655):495–9.

  41. 41.

    Neubert NJ, Schmittnaegel M, Bordry N, Nassiri S, Wald N, Martignier C, et al. T cell-induced CSF1 promotes melanoma resistance to PD1 blockade. Sci Transl Med. 2018;10(436).

  42. 42.

    Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11(11):3887–95.

  43. 43.

    Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.

  44. 44.

    Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999 Dec;5(12):1365–9.

  45. 45.

    • Taube JM, Anders RA, Young GD, Xu H, Sharma R, TL MM, et al. Colocalization of inflammatory response with B7-H1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4(127):127ra37 Describes PD-L1 staining in melanoma as a marker of PD-1 response.

  46. 46.

    Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.

  47. 47.

    Herbst RS, Soria J-C, Kowanetz M, Fine GD, Hamid O, Gordon MS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563–7.

  48. 48.

    Daud AI, Wolchok JD, Robert C, Hwu W-J, Weber JS, Ribas A, et al. Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(34):4102–9.

  49. 49.

    Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015 Jan 22;372(4):320–30.

  50. 50.

    Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–33.

  51. 51.

    Carlino MS, Long GV, Schadendorf D, Robert C, Ribas A, Richtig E, et al. Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: a randomised clinical trial. Eur J Cancer Oxf Engl. 2018;101:236–43.

  52. 52.

    Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379(8):722–30.

  53. 53.

    Hodi FS, Chiarion-Sileni V, Gonzalez R, Grob J-J, Rutkowski P, Cowey CL, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19(11):1480–92.

  54. 54.

    Adam J, Le Stang N, Rouquette I, Cazes A, Badoual C, Pinot-Roussel H, et al. Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer. Ann Oncol Off J Eur Soc Med Oncol. 2018;29(4):953–8.

  55. 55.

    Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.

  56. 56.

    Lee J-L, Ziobro M, Gafanov R, Matveev VB, Suarez C, Donskov F, et al. KEYNOTE-427 cohort B: first-line pembrolizumab (pembro) monotherapy for advanced non–clear cell renal cell carcinoma (NCC-RCC). J Clin Oncol. 2019;37(15_suppl):4569.

  57. 57.

    Thomas NE, Busam KJ, From L, Kricker A, Armstrong BK, Anton-Culver H, et al. Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(33):4252–9.

  58. 58.

    Huh JW, Lee JH, Kim HR. Prognostic significance of tumor-infiltrating lymphocytes for patients with colorectal cancer. Arch Surg. 2012;147(4):366–72.

  59. 59.

    Zeng D-Q, Yu Y-F, Ou Q-Y, Li X-Y, Zhong R-Z, Xie C-M, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer. Oncotarget. 2016;7(12):13765–81.

  60. 60.

    • Tumeh PC, Harview CL, Yearley JH, Shintaku IP, EJM T, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71 Describes T cell proliferation in response to PD-1 blockade.

  61. 61.

    • Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell. 2014;26(5):638–52 Shows the importance of DC in determining an inflamed tumor.

  62. 62.

    Spranger S, Dai D, Horton B, Gajewski TF. Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell. 2017;31(5):711–23 e4.

  63. 63.

    Binnewies M, Mujal AM, Pollack JL, Combes AJ, Hardison EA, Barry KC, et al. Unleashing type-2 dendritic cells to drive protective antitumor CD4+ T cell immunity. Cell. 2019;177(3):556–71 e16.

  64. 64.

    Thommen DS, Koelzer VH, Herzig P, Roller A, Trefny M, Dimeloe S, et al. A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade. Nat Med. 2018;24(7):994–1004.

  65. 65.

    Scott AC, Dündar F, Zumbo P, Chandran SS, Klebanoff CA, Shakiba M, et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature. 2019;571(7764):270–4.

  66. 66.

    Khan O, Giles JR, McDonald S, Manne S, Ngiow SF, Patel KP, et al. TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion. Nature. 2019;571(7764):211–8.

  67. 67.

    Yao C, Sun H-W, Lacey NE, Ji Y, Moseman EA, Shih H-Y, et al. Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection. Nat Immunol. 2019;20(7):890–901.

  68. 68.

    Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, et al. Defining “T cell exhaustion.”. Nat Rev Immunol. 2019;19(11):665–74.

  69. 69.

    Samstein RM, Lee C-H, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51(2):202–6.

  70. 70.

    Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.

  71. 71.

    McGranahan N, Furness AJS, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–9.

  72. 72.

    Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim S-W, Carcereny Costa E, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381(21):2020–31.

  73. 73.

    Algazi AP, Tsai KK, Shoushtari AN, Munhoz RR, Eroglu Z, Piulats JM, et al. Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer. 2016;122(21):3344–53.

  74. 74.

    Johnson DB, Bao R, Ancell KK, Daniels AB, Wallace D, Sosman JA, et al. Response to anti-PD-1 in uveal melanoma without high-volume liver metastasis. J Natl Compr Cancer Netw JNCCN. 2019;17(2):114–7.

  75. 75.

    Mandal R, Samstein RM, Lee K-W, Havel JJ, Wang H, Krishna C, et al. Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response. Science. 2019;364(6439):485–91.

  76. 76.

    Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13.

  77. 77.

    Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.

  78. 78.

    Germano G, Lamba S, Rospo G, Barault L, Magrì A, Maione F, et al. Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth. Nature. 2017;552(7683):116–20.

  79. 79.

    Eroglu Z, Zaretsky JM, Hu-Lieskovan S, Kim DW, Algazi A, Johnson DB, et al. High response rate to PD-1 blockade in desmoplastic melanomas. Nature. 2018;553(7688):347–50.

  80. 80.

    Kaunitz GJ, Cottrell TR, Lilo M, Muthappan V, Esandrio J, Berry S, et al. Melanoma subtypes demonstrate distinct PD-L1 expression profiles. Lab Investig J Tech Methods Pathol. 2017;97(9):1063–71.

  81. 81.

    Jayaraman SS, Rayhan DJ, Hazany S, Kolodney MS. Mutational landscape of basal cell carcinomas by whole-exome sequencing. J Invest Dermatol. 2014;134(1):213–20.

  82. 82.

    Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P, McLaren S, et al. Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science. 2015;348(6237):880–6.

  83. 83.

    Falchook GS, Leidner R, Stankevich E, Piening B, Bifulco C, Lowy I, et al. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer. 2016;4:70.

  84. 84.

    Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379(4):341–51.

  85. 85.

    Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med. 2016;374(26):2542–52.

  86. 86.

    Goh G, Walradt T, Markarov V, Blom A, Riaz N, Doumani R, et al. Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy. Oncotarget. 2016;7(3):3403–15.

  87. 87.

    Martens A, Wistuba-Hamprecht K, Geukes Foppen M, Yuan J, Postow MA, Wong P, et al. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin Cancer Res Off J Am Assoc Cancer Res. 2016;22(12):2908–18.

  88. 88.

    Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, et al. Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin Cancer Res Off J Am Assoc Cancer Res. 2016;22(22):5487–96.

  89. 89.

    Rosner S, Kwong E, Shoushtari AN, Friedman CF, Betof AS, Brady MS, et al. Peripheral blood clinical laboratory variables associated with outcomes following combination nivolumab and ipilimumab immunotherapy in melanoma. Cancer Med. 2018;7(3):690–7.

  90. 90.

    Caballero S, Pamer EG. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annu Rev Immunol. 2015;33(1):227–56.

  91. 91.

    Schwabe RF, Jobin C. The microbiome and cancer. Nat Rev Cancer. 2013;13(11):800–12.

  92. 92.

    Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A, Wargo JA. The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell. 2018;33(4):570–80.

  93. 93.

    Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97–103.

  94. 94.

    Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre M-L, et al. The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104–8.

  95. 95.

    Wargo JA, Gopalakrishnan V, Spencer C, Karpinets T, Reuben A, Andrews MC, et al. Association of the diversity and composition of the gut microbiome with responses and survival (PFS) in metastatic melanoma (MM) patients (pts) on anti-PD-1 therapy. J Clin Oncol. 2017;35(15_suppl):3008.

  96. 96.

    Dubin K, Callahan MK, Ren B, Khanin R, Viale A, Ling L, et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun. 2016;7(1):1–8.

Download references

Author information

Correspondence to Adil I. Daud.

Ethics declarations

Conflict of Interest

Christopher G. Twitty declares that he has no conflict of interest. Laura A. Huppert declares that she has no conflict of interest. Adil I. Daud has received research funding from Merck, OncoSec, Bristol-Myers Squibb, Incyte, Checkmate, and Pfizer.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Melanoma

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Twitty, C.G., Huppert, L.A. & Daud, A.I. Prognostic Biomarkers for Melanoma Immunotherapy. Curr Oncol Rep 22, 25 (2020). https://doi.org/10.1007/s11912-020-0886-z

Download citation

Keywords

  • Immune checkpoint inhibitors
  • Programmed death-1 (PD-1)
  • Programmed death ligand-1 (PD-L1)
  • Exhausted T cells (Tex)
  • Tumor microenvironment (TME)
  • Memory T cells (Tmem)
  • Tumor mutation burden
  • Circulating tumor DNA