Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12–49.

PubMed  Google Scholar 

Garbe C, Keim U, Gandini S, Amaral T, Katalinic A, Hollezcek B, Martus P, Flatz L, Leiter U, Whiteman D. Epidemiology of cutaneous melanoma and keratinocyte cancer in white populations 1943–2036. Eur J Cancer. 2021;152:18–25.

PubMed  Google Scholar 

Miller KD, Fidler-Benaoudia M, Keegan TH, Hipp HS, Jemal A, Siegel RL. Cancer statistics for adolescents and young adults, 2020. CA Cancer J Clin. 2020;70(6):443–59.

PubMed  Google Scholar 

Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.

CAS  PubMed  PubMed Central  Google Scholar 

Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000;18(1):158–66.

CAS  PubMed  Google Scholar 

Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph R, Weber JS, et al. Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Ann Oncol. 2019;30(4):582–8.

CAS  PubMed  PubMed Central  Google Scholar 

Wolchok JD, Chiarion-Sileni V, Rutkowski P, Cowey CL, Schadendorf D, Wagstaff J, Queirolo P, Dummer R, Butler MO, Hill AG, et al. Final, 10-year outcomes with nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2025;392(1):11–22.

CAS  PubMed  Google Scholar 

Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutierrez E, Rutkowski P, Gogas HJ, Lao CD, De Menezes JJ, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med. 2022;386(1):24–34.

CAS  PubMed  PubMed Central  Google Scholar 

Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, Thomas SS, Domingo-Musibay E, Pavlick AC, Whitman ED, et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J Clin Oncol. 2021;39(24):2656–66.

CAS  PubMed  PubMed Central  Google Scholar 

Rohaan MW, Borch TH, van den Berg JH, Met O, Kessels R, Geukes Foppen MH, Stoltenborg Granhoj J, Nuijen B, Nijenhuis C, Jedema I, et al. Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma. N Engl J Med. 2022;387(23):2113–25.

CAS  PubMed  Google Scholar 

Blank CU, Lucas MW, Scolyer RA, van de Wiel BA, Menzies AM, Lopez-Yurda M, Hoeijmakers LL, Saw RPM, Lijnsvelt JM, Maher NG, et al. Neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma. N Engl J Med. 2024.

Patel SP, Othus M, Chen Y, Wright GP Jr, Yost KJ, Hyngstrom JR, Hu-Lieskovan S, Lao CD, Fecher LA, Truong TG, et al. Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med. 2023;388(9):813–23.

CAS  PubMed  PubMed Central  Google Scholar 

Bottomley A, Coens C, Mierzynska J, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(5):655–64.

CAS  PubMed  Google Scholar 

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381(16):1535–46.

CAS  PubMed  Google Scholar 

Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158–68.

CAS  PubMed  Google Scholar 

Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214–8.

CAS  PubMed  PubMed Central  Google Scholar 

Buchbinder EI, Weirather JL, Manos M, Quattrochi BJ, Sholl LM, Brennick RC, Bowling P, Bailey N, Magarace L, Ott PA, et al. Characterization of genetics in patients with mucosal melanoma treated with immune checkpoint blockade. Cancer Med. 2021;10(8):2627–35.

CAS  PubMed  PubMed Central  Google Scholar 

Robertson AG, Shih J, Yau C, Gibb EA, Oba J, Mungall KL, Hess JM, Uzunangelov V, Walter V, Danilova L, et al. Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell. 2017;32(2):204–220 e215.

Viros A, Sanchez-Laorden B, Pedersen M, Furney SJ, Rae J, Hogan K, Ejiama S, Girotti MR, Cook M, Dhomen N, et al. Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53. Nature. 2014;511(7510):478–82.

CAS  PubMed  PubMed Central  Google Scholar 

Mitra D, Luo X, Morgan A, Wang J, Hoang MP, Lo J, Guerrero CR, Lennerz JK, Mihm MC, Wargo JA, et al. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature. 2012;491(7424):449–53.

CAS  PubMed  PubMed Central  Google Scholar 

Pavey S, Russell T, Gabrielli B. G2 phase cell cycle arrest in human skin following UV irradiation. Oncogene. 2001;20(43):6103–10.

CAS  PubMed  Google Scholar 

Birkeland E, Zhang S, Poduval D, Geisler J, Nakken S, Vodak D, Meza-Zepeda LA, Hovig E, Myklebost O, Knappskog S, et al. Patterns of genomic evolution in advanced melanoma. Nat Commun. 2018;9(1):2665.

CAS  PubMed  PubMed Central  Google Scholar 

Harbst K, Lauss M, Cirenajwis H, Isaksson K, Rosengren F, Torngren T, Kvist A, Johansson MC, Vallon-Christersson J, Baldetorp B, et al. Multiregion whole-exome sequencing uncovers the genetic evolution and mutational heterogeneity of early-stage metastatic melanoma. Cancer Res. 2016;76(16):4765–74.

CAS  PubMed  Google Scholar 

Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A, Dummer R, North J, Pincus L, Ruben B, et al. The genetic evolution of melanoma from precursor lesions. N Engl J Med. 2015;373(20):1926–36.

PubMed  Google Scholar 

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

CAS  PubMed  Google Scholar 

Xie N, Shen G, Gao W, Huang Z, Huang C, Fu L. Neoantigens: promising targets for cancer therapy. Signal Transduct Target Ther. 2023;8(1):9.

CAS  PubMed  PubMed Central  Google Scholar 

Neefjes J, Jongsma ML, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol. 2011;11(12):823–36.

CAS  PubMed  Google Scholar 

Higgins JP, Bernstein MB, Hodge JW. Enhancing immune responses to tumor-associated antigens. Cancer Biol Ther. 2009;8(15):1440–9.

CAS  PubMed  Google Scholar 

Dreno B, Thompson JF, Smithers BM, Santinami M, Jouary T, Gutzmer R, Levchenko E, Rutkowski P, Grob JJ, Korovin S, et al. MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19(7):916–29.

CAS  PubMed  Google Scholar 

Gutzmer R, Rivoltini L, Levchenko E, Testori A, Utikal J, Ascierto PA, Demidov L, Grob JJ, Ridolfi R, Schadendorf D, et al. Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: results of a phase I dose escalation study. ESMO Open. 2016;1(4): e000068.

CAS  PubMed  PubMed Central  Google Scholar 

Kyte JA, Aamdal S, Dueland S, Saeboe-Larsen S, Inderberg EM, Madsbu UE, Skovlund E, Gaudernack G, Kvalheim G. Immune response and long-term clinical outcome in advanced melanoma patients vaccinated with tumor-mRNA-transfected dendritic cells. Oncoimmunology. 2016;5(11): e1232237.

PubMed  PubMed Central  Google Scholar 

Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004;10(9):909–15.

CAS  PubMed  PubMed Central  Google Scholar 

Schwartzentruber DJ, Lawson D, Richards J, Conry RM, Miller D, Triesman J, Gailani F, Riley LB, Vena D, Hwu P. A phase III multi-institutional randomized study of immunization with the gp100: 209–217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. J Clin Oncol. 2009;27(18_suppl):CRA9011.

De Plaen E, Lurquin C, Van Pel A, Mariame B, Szikora JP, Wolfel T, Sibille C, Chomez P, Boon T. Immunogenic (tum-) variants of mouse tumor P815: cloning of the gene of tum- antigen P91A and identification of the tum- mutation. Proc Natl Acad Sci USA. 1988;85(7):2274–8.

PubMed  PubMed Central  Google Scholar 

Shao XM, Bhattacharya R, Huang J, Sivakumar IKA, Tokheim C, Zheng L, Hirsch D, Kaminow B, Omdahl A, Bonsack M, et al. High-throughput prediction of MHC class I and II neoantigens with MHCnuggets. Cancer Immunol Res. 2020;8(3):396–408.

CAS  PubMed  Google Scholar 

Yang W, Lee KW, Srivastava RM, Kuo F, Krishna C, Chowell D, Makarov V, Hoen D, Dalin MG, Wexler L, et al. Immunogenic neoantigens derived from gene fusions stimulate T cell responses. Nat Med. 2019;25(5):767–75.

CAS  PubMed  PubM