Onkologie. 2026:20(1):6-10 | DOI: 10.36290/xon.2026.001

New trends in melanoma immunotherapy

Linda Řandová, Ondřej Kodet
Dermatovenerologická klinika, 1. LF UK a VFN, Praha

Immunotherapy with checkpoint inhibitors has long been one of the mainstays of melanoma therapy. Despite the long-term therapeutic response that can be achieved, many patients experience lower rates of therapeutic response or failure even after an initial good therapeutic response. A large percentage of patients do not respond to this form of treatment. New clinical trials are currently underway to strengthen this form of treatment and overcome some resistance mechanisms. The greatest progress in new trends in melanoma immunotherapy is documented in the use of tumour mRNA vaccines, adoptive cell therapy, and intratumoral drug administration. Although the data available so far offer promising prospects for melanoma treatment, it will be necessary to wait for longer-term follow-up from large clinical trials.

Keywords: melanoma, checkpoint inhibitors, mRNA vaccines, adoptive cell therapy, intratumoral immunotherapy, microbiome.

Accepted: March 2, 2026; Published: March 16, 2026  Show citation

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Řandová L, Kodet O. New trends in melanoma immunotherapy. Onkologie. 2026;20(1):6-10. doi: 10.36290/xon.2026.001.
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    References

    1. Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. [Internet]. [cited 2026 Jan 19]. 2025;392(1):11-22. Available from: https://pubmed.ncbi.nlm.nih.gov/39282897/. Go to original source... Go to PubMed...
    2. Arnold M, de Vries E, Whiteman DC, et al. Global burden of cutaneous melanoma attributable to ultraviolet radiation in 2012. Int J Cancer. [Internet]. [cited 2026 Jan 22]. 2018;143(6):1305-1314. Available from: https://pubmed.ncbi.nlm.nih.gov/29659012/. Go to original source... Go to PubMed...
    3. Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. [Internet]. [cited 2026 Jan 22]. 2013;500(7463):415-421. Available from: https://pubmed.ncbi.nlm.nih.gov/23945592/. Go to original source... Go to PubMed...
    4. Engels EA, Pfeiffer RM, Fraumeni JF, et al. Spectrum of Cancer Risk among U.S. Solid Organ Transplant Recipients: The Transplant Cancer Match Study. JAMA. [Internet]. [cited 2026 Jan 22]. 2011;306(17):1891. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC3310893/. Go to original source... Go to PubMed...
    5. Botella-Estrada R, Traves V, Requena C, et al. Correlation of histologic regression in primary melanoma with sentinel node status. JAMA Dermatol. [Internet]. [cited 2026 Jan 22]. 2014;150(8):828-835. Available from: https://pubmed.ncbi.nlm.nih.gov/24898614/. Go to original source... Go to PubMed...
    6. Aung PP, Nagarajan P, Prieto VG. Regression in primary cutaneous melanoma: Etiopathogenesis and clinical significance. Laboratory Investigation. [Internet]. [cited 2026 Jan 22]. 2017;97(6):657-668. Available from: https://pubmed.ncbi.nlm.nih.gov/28240749/. Go to original source... Go to PubMed...
    7. Wagner NB, Knierim SM, Luttermann F, et al. Histopathologic regression in patients with primary cutaneous melanoma undergoing sentinel lymph node biopsy is associated with favorable survival and, after metastasis, with improved progression-free survival on immune checkpoint inhibitor therapy: A si…. J Am Acad Dermatol. [Internet]. [cited 2026 Jan 22]. 2024;90(4):739-748. Available from: https://pubmed.ncbi.nlm.nih.gov/38043594/. Go to original source... Go to PubMed...
    8. Alspach E, Lussier DM, Miceli AP, et al. MHC-II neoantigens shape tumour immunity and response to immunotherapy. Nature. [Internet]. [cited 2026 Jan 24]. 2019;574(7780):696-701. Available from: https://pubmed.ncbi.nlm.nih.gov/31645760/. Go to original source... Go to PubMed...
    9. Wu Y, Biswas D, Swanton C. Impact of cancer evolution on immune surveillance and checkpoint inhibitor response. Semin Cancer Biol. [Internet]. [cited 2026 Jan 24]. 2022;84:89-102. Available from: https://pubmed.ncbi.nlm.nih.gov/33631295/. Go to original source... Go to PubMed...
    10. Hashimoto M, Kamphorst AO, Im SJ, et al. CD8 T Cell Exhaustion in Chronic Infection and Cancer: Opportunities for Interventions. Annu Rev Med. [Internet]. [cited 2026 Jan 24]. 2018;69:301-318. Available from: https://pubmed.ncbi.nlm.nih.gov/29414259/. Go to original source... Go to PubMed...
    11. van der Leun AM, Thommen DS, Schumacher TN. CD8+ T cell states in human cancer: insights from single-cell analysis. Nat Rev Cancer. [Internet]. [cited 2026 Jan 24]. 2020;20(4):218-232. Available from: https://pubmed.ncbi.nlm.nih.gov/32024970/. Go to original source... Go to PubMed...
    12. Oliveira G, Stromhaug K, Cieri N, et al. Landscape of helper and regulatory antitumour CD4+ T cells in melanoma. Nature. [Internet]. [cited 2026 Jan 24]. 2022;605(7910):532-538. Available from: https://pubmed.ncbi.nlm.nih.gov/35508657/. Go to original source... Go to PubMed...
    13. Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. [Internet]. [cited 2026 Jan 24]. 2020;20(11):651-668. Available from: https://pubmed.ncbi.nlm.nih.gov/32433532/. Go to original source... Go to PubMed...
    14. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin. [Internet]. [cited 2026 Jan 24]. 2023;73(1):17-48. Available from: https://pubmed.ncbi.nlm.nih.gov/36633525/. Go to original source... Go to PubMed...
    15. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472-492. Go to original source... Go to PubMed...
    16. Dummer R, Hauschild A, Santinami M, et al. Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma. N Engl J Med. [Internet]. [cited 2026 Jan 24]. 2020;383(12):1139-1148. Available from: https://pubmed.ncbi.nlm.nih.gov/32877599/. Go to original source... Go to PubMed...
    17. Luke JJ, Ascierto PA, Khattak MA, et al. Pembrolizumab Versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE-716 Study. J Clin Oncol. [Internet]. [cited 2026 Jan 24]. 2024;42(14):1619-1624. Available from: https://pubmed.ncbi.nlm.nih.gov/38452313/. Go to original source... Go to PubMed...
    18. Eggermont AMM, Blank CU, Mandalà M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. [Internet]. [cited 2026 Jan 24]. 2021;22(5):643-654. Available from: https://pubmed.ncbi.nlm.nih.gov/33857412/. Go to original source... Go to PubMed...
    19. Eggermont AM, Kicinski M, Blank CU, et al. Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial. Eur J Cancer. [Internet]. [cited 2026 Jan 24]. 2024 Nov 1;211. Available from: https://www.ejcancer.com/action/showFullText?pii=S0959804924009833. Go to original source... Go to PubMed...
    20. Larkin J, Del Vecchio M, Mandalá M, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results from Check­Mate 238. Clin Cancer Res. [Internet]. [cited 2026 Jan 24]. 2023;29(17):3352-3361. Available from: https://pubmed.ncbi.nlm.nih.gov/37058595/. Go to original source... Go to PubMed...
    21. Prkačin I, Brkić A, Pondeljak N, et al. Adjuvant Immunotherapy in Stage IIB/IIC Melanoma: Current Evidence and Future Directions. Biomedicines. [Internet]. [cited 2026 Jan 24]. 2025;13(8). Available from: https://pubmed.ncbi.nlm.nih.gov/40868149/. Go to original source... Go to PubMed...
    22. Mok S, Liu H, Çobanoğlu DA, et al. Anti-CTLA-4 generates greater memory response than anti-PD-1 via TCF-1. Proc Natl Acad Sci U S A. [Internet]. [cited 2026 Jan 24]. 2025;14:122(2). Available from: https://www.pnas.org/doi/pdf/10.1073/pnas.2418985122. Go to original source... Go to PubMed...
    23. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. J Clin Oncol [Internet]. [cited 2026 Jan 24]. 2022;40(2):127-137. Available from: https://pubmed.ncbi.nlm.nih.gov/34818112/. Go to original source... Go to PubMed...
    24. Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med [Internet]. 2015 Sep 24 [cited 2026 Jan 24];373(13):1270-1271. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26398076. Go to original source...
    25. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. J Clin Oncol [Internet]. [cited 2026 Jan 24]. 2022;40(2):127-37. Available from: https://pubmed.ncbi.nlm.nih.gov/34818112/. Go to original source... Go to PubMed...
    26. Long GV, Larkin J, Schadendorf D, et al. Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma. J Clin Oncol. [Internet]. [cited 2026 Jan 24]. 2025;43(8):938-948. Available from: https://pubmed.ncbi.nlm.nih.gov/39504507/. Go to original source... Go to PubMed...
    27. Ellebaek E, Khan S, Bastholt L, et al. PD-L1 is a biomarker of real-world clinical outcomes for anti-CTLA-4 plus anti-PD-1 or anti-PD-1 monotherapy in metastatic melanoma. Eur J Cancer. [Internet]. [cited 2026 Jan 24]. 2024 Feb 1;198. Available from: https://pubmed.ncbi.nlm.nih.gov/38171116/. Go to original source... Go to PubMed...
    28. van Not OJ, van den Eertwegh AJM, Jalving H, et al. Long-Term Survival in Patients With Advanced Melanoma. JAMA Netw Open. [Internet]. [cited 2026 Jan 24]. 2024;7(8):e2426641. Available from: https://pubmed.ncbi.nlm.nih.gov/39141388/. Go to original source... Go to PubMed...
    29. Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. [Internet]. [cited 2026 Jan 24]. 2022;386(1):24-34. Available from: https://pubmed.ncbi.nlm.nih.gov/34986285/. Go to original source... Go to PubMed...
    30. Long GV, Hodi SF, Lipson EJ, et al. Overall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma. NEJM evidence. [Internet]. 28 [cited 2026 Jan 24]. 2023;2(4). Available from: https://pubmed.ncbi.nlm.nih.gov/38320023/.
    31. Laila UE, An W, Xu ZX. Emerging prospects of mRNA cancer vaccines: mechanisms, formulations, and challenges in cancer immunotherapy. Front Immunol. [Internet]. [cited 2026 Jan 25]. 2024;15. Available from: https://pubmed.ncbi.nlm.nih.gov/39654897/. Go to original source... Go to PubMed...
    32. Pardi N, Krammer F. mRNA vaccines for infectious diseases - advances, challenges and opportunities. Nat Rev Drug Discov. [Internet]. [cited 2026 Jan 25]. 2024;23(11):838-861. Available from: https://pubmed.ncbi.nlm.nih.gov/39367276/. Go to original source... Go to PubMed...
    33. Fan T, Zhang M, Yang J, et al. Therapeutic cancer vaccines: advancements, challenges, and prospects. Signal Transduct Target Ther. [Internet]. [cited 2026 Jan 25]. 2023;8(1). Available from: https://pubmed.ncbi.nlm.nih.gov/38086815/. Go to original source... Go to PubMed...
    34. Zoroddu S, Bagella L. Next-Generation mRNA Vaccines in Melanoma: Advances in Delivery and Combination Strategies. Cells. [Internet]. [cited 2026 Jan 25]. 2025;14(18):1476. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12468083/. Go to original source... Go to PubMed...
    35. Weber JS, Carlino MS, Khattak A, et al. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. The Lancet. [Internet]. [cited 2026 Jan 25]. 2024;403(10427):632-644. Available from: https://www.thelancet.com/action/showFullText?pii=S0140673623022687. Go to original source... Go to PubMed...
    36. Schuster SJ, Svoboda J, Chong EA, et al. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. [Internet]. 28 [cited 2026 Jan 25]. 2017;377(26):2545-2554. Available from: https://pubmed.ncbi.nlm.nih.gov/29226764/. Go to original source... Go to PubMed...
    37. June CH, O'Connor RS, Kawalekar OU, et al. CAR T cell immunotherapy for human cancer. Science [Internet]. [cited 2026 Jan 25]. 2018;359(6382):1361-1365. Available from: https://pubmed.ncbi.nlm.nih.gov/29567707/. Go to original source... Go to PubMed...
    38. Wermke M, Araujo DM, Chatterjee M, et al. Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial. Nat Med. [Internet]. [cited 2026 Jan 25]. 2025;31(7):2365-2374. Available from: https://pubmed.ncbi.nlm.nih.gov/40205198/. Go to original source... Go to PubMed...
    39. Wermke M, Araujo DM, Chatterjee M, et al. Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial. Nat Med [Internet]. [cited 2026 Jan 25]. 2025;31(7):2365. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12283372/. Go to original source... Go to PubMed...
    40. Jogalekar MP, Rajendran RL, Khan F,et al. CAR T-Cell-Based gene therapy for cancers: new perspectives, challenges, and clinical developments. Front Immunol. 2022 Jul 22;13. Go to original source... Go to PubMed...
    41. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. [Internet]. [cited 2026 Jan 25]. 2021 Apr 1;11(4). Available from: https://pubmed.ncbi.nlm.nih.gov/33824268/. Go to original source... Go to PubMed...
    42. Davies D, Kamdar S, Woolf R, et al. PD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy. Nat Cancer. [Internet]. [cited 2026 Jan 25]. 2024;5(3):420-432. Available from: https://pubmed.ncbi.nlm.nih.gov/38172341/. Go to original source... Go to PubMed...
    43. Bonini C, Mondino A. Adoptive T-cell therapy for cancer: The era of engineered T cells. Eur J Immunol. 2015;45(9):2457-2469. Go to original source... Go to PubMed...
    44. de Vries NL, van de Haar J, Veninga V, et al. γδ T cells are effectors of immunotherapy in cancers with HLA class I defects. Nature. [Internet]. [cited 2026 Jan 25]. 2023;613(7945):743-750. Available from: https://pubmed.ncbi.nlm.nih.gov/36631610/. Go to original source... Go to PubMed...
    45. LaRocca CJ, Warner SG. Oncolytic viruses and checkpoint inhibitors: combination therapy in clinical trials. Clin Transl Med [Internet]. [cited 2026 Jan 25]. 2018;7(1). Available from: https://pubmed.ncbi.nlm.nih.gov/30426287/. Go to original source... Go to PubMed...
    46. Wang X, Zhang H, XinZhang,et al. Abscopal effect: from a rare phenomenon to a new frontier in cancer therapy. Biomark Res [Internet]. [cited 2026 Jan 25]. 2024;12(1). Available from: https://pubmed.ncbi.nlm.nih.gov/39228005/. Go to original source... Go to PubMed...
    47. Thomas S, Kuncheria L, Roulstone V, et al. Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J Immunother Cancer [Internet]. [cited 2026 Jan 25]. 2019;7(1):214. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6689178/. Go to original source... Go to PubMed...
    48. Wong MK, Milhem MM, Sacco JJ, et al. RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE). Journal of Clinical Oncology [Internet]. [cited 2026 Jan 25]. 2025;43(33):3589. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12622257/. Go to original source... Go to PubMed...
    49. Kähler KC, Hassel JC, Ziemer M, et al. Neoadjuvant intralesional targeted immunocytokines (daromun) in stage III melanoma. Ann Oncol [Internet]. [cited 2026 Jan 25]. 2025;36(10):1166-1177. Available from: https://pubmed.ncbi.nlm.nih.gov/40633690/. Go to original source... Go to PubMed...
    50. Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res [Internet]. [cited 2026 Jan 26]. 2020;30(6):492-506. Available from: https://pubmed.ncbi.nlm.nih.gov/32433595/. Go to original source... Go to PubMed...
    51. Simpson RC, Shanahan ER, Scolyer RA, et al. Towards modulating the gut microbiota to enhance the efficacy of immune-checkpoint inhibitors. Nat Rev Clin Oncol. [Internet]. [cited 2026 Jan 26]. 2023;20(10):697-715. Available from: https://pubmed.ncbi.nlm.nih.gov/37488231/. Go to original source... Go to PubMed...
    52. Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science (1979). [Internet]. [cited 2020 Sep 8]. 2018;359(6371):97-103. Available from: https://pubmed.ncbi.nlm.nih.gov/29097493/. Go to original source... Go to PubMed...
    53. Pinato DJ, Howlett S, Ottaviani D, et al. Association of Prior Antibiotic Treatment With Survival and Response to Immune Checkpoint Inhibitor Therapy in Patients With Cancer. JAMA Oncol. [Internet]. [cited 2026 Jan 26]. 2019;5(12):1774-1778. Available from: https://pubmed.ncbi.nlm.nih.gov/31513236/. Go to original source... Go to PubMed...
    54. Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. [Internet]. [cited 2026 Jan 26]. 2018;359(6371):97-103. Available from: https://pubmed.ncbi.nlm.nih.gov/29097493/. Go to original source... Go to PubMed...
    55. Davar D, Dzutsev AK, McCulloch JA, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. [Internet]. [cited 2026 Jan 26]. 2021;371(6529):595-602. Available from: https://pubmed.ncbi.nlm.nih.gov/33542131/. Go to original source... Go to PubMed...
    56. Baruch EN, Youngster I, Ben-Betzalel G, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science [Internet]. [cited 2026 Jan 26] 2021;371(6529):602-609. Available from: https://pubmed.ncbi.nlm.nih.gov/33303685/. Go to original source... Go to PubMed...
    57. Routy B, Lenehan JG, Miller WH, et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial. Nat Med. [Internet]. [cited 2026 Jan 26]. 2023;29(8):2121-2132. Available from: https://pubmed.ncbi.nlm.nih.gov/37414899/. Go to original source... Go to PubMed...

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