: Immunotherapy with immune checkpoint inhibitors (ICIs) is a promising therapeutic schedule in advanced solid cancers. In this review, clinical trials from highly reputable journals are interpreted for safety and efficacy evaluation of the common anti-programmed death-1 (PD-1) inhibitor nivolumab and/or the most known anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitor ipilimumab in advanced melanoma. Current progress in the field of melanoma immunotherapy is the focus of this review. Solo nivolumab and combo nivolumab-ipilimumab show higher responses compared to solo ipilimumab or chemotherapy. BRAF and programmed death-ligand 1 (PDL1) expression states are seemingly not reliable biomarkers of response to ICI therapy in melanoma. Solo ipilimumab and particularly a combination of nivolumab-ipilimumab show higher adverse events (AEs) compared with solo nivolumab or chemotherapy. Besides, ICI therapy is safer in mucosal melanoma, but its efficacy is higher in the cutaneous subtype. Patients receiving combination regimens who are experiencing serious AEs can discontinue such regimens until recovery and still maintain clinical benefits. To conclude, combo nivolumab-ipilimumab represents more therapeutic advantages compared with solo nivolumab or ipilimumab, but the rate of AEs is higher for combination regimens. Resistance to combo nivolumab-ipilimumab demands the application of novel approaches to go with ICIs in melanoma immunotherapy. Immunogenic agents, alternative immune checkpoints, vaccination, oncolytic viruses, extracellular vesicles (EVs) and fecal microbiome transplantation (FMT) are novel strategies in patients developing ICI resistance.

中文翻译：

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人类黑色素瘤的免疫治疗：过去、现在、未来

：免疫检查点抑制剂（ICIs）的免疫治疗是晚期实体癌的一种有前景的治疗方案。在这篇综述中，来自知名期刊的临床试验被解释为常见的抗程序性死亡 1 (PD-1) 抑制剂纳武单抗和/或最著名的抗细胞毒性 T 淋巴细胞相关抗原 4 的安全性和有效性评估（ CTLA-4）抑制剂伊匹单抗治疗晚期黑色素瘤。黑色素瘤免疫治疗领域的最新进展是本次综述的重点。与单独的伊匹单抗或化疗相比，单独的纳武单抗和组合纳武单抗-伊匹单抗显示出更高的反应。BRAF 和程序性死亡配体 1 (PDL1) 表达状态似乎并不是黑色素瘤 ICI 治疗反应的可靠生物标志物。与单独的纳武单抗或化疗相比，单独的伊匹单抗，特别是纳武单抗-伊匹木单抗的组合显示出更高的不良事件（AE）。此外，ICI治疗粘膜黑色素瘤更安全，但对于皮肤亚型的疗效更高。接受联合治疗方案且出现严重 AE 的患者可以停止此类治疗方案直至康复，并仍能保持临床获益。总之，与单独使用纳武单抗或伊匹单抗相比，纳武单抗-伊匹单抗组合具有更多的治疗优势，但联合方案的 AE 发生率更高。对纳武单抗-伊匹单抗组合的耐药性需要在黑色素瘤免疫治疗中应用新方法与 ICI 相结合。免疫原性药物、替代免疫检查点、疫苗接种、溶瘤病毒、细胞外囊泡 (EV) 和粪便微生物组移植 (FMT) 是治疗 ICI 耐药患者的新策略。