Abstract：
The use of immunotherapy in the treatment of advanced and high-risk melanoma has led to a striking improvement in outcomes. Although the incidence of melanoma has continued to rise, median survival has improved from approximately 6 months to nearly 6 years for patients with advanced inoperable stage IV disease. Recent understanding of the tumor microenvironment and its interplay with the immune system has led to the explosive development of novel immunotherapy treatments. Since the approval of the therapeutic cytokines interleukin-2 and interferon alfa-2 in the 1990s, the development of novel immune checkpoint inhibitors (ICIs), oncolytic virus therapy, and modulators of the tumor microenvironment have given way to a new era in melanoma treatment. Monoclonal antibodies directed at programmed cell death protein 1 receptor (PD-1) and its ligand (PDL-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) have provided robust activation of the adaptive immune system, restoring immune surveillance leading to host tumor recognition and destruction. Multiple other immunomodulatory therapeutics are under investigation to overcome resistance to ICI therapy, including the toll-like receptor-9 (TLR-9) and 7/8 (TLR-7/8) agonists, stimulator of interferon genes (STING) agonists, and fecal microbiota transplantation. In this review, we focus on the recent advances in immunotherapy for the treatment of melanoma and provide an update on novel therapies currently under investigation.
摘要：
在晚期和高风险黑色素瘤的治疗中使用免疫疗法已导致结果的显着改善。尽管黑色素瘤的发病率持续上升,晚期无法手术的IV期疾病患者的中位生存期从约6个月提高到近6年.最近对肿瘤微环境及其与免疫系统相互作用的理解导致了新型免疫疗法的爆炸性发展。自1990年代批准治疗性细胞因子白介素-2和干扰素α-2以来，新型免疫检查点抑制剂（ICIs）的开发，溶瘤病毒治疗，和肿瘤微环境的调节剂已经让位于黑色素瘤治疗的新时代。针对程序性细胞死亡蛋白1受体(PD-1)及其配体(PDL-1)的单克隆抗体,细胞毒性T淋巴细胞相关蛋白4（CTLA-4），和淋巴细胞激活基因3（LAG-3）提供了适应性免疫系统的强大激活，恢复导致宿主肿瘤识别和破坏的免疫监视。其他多种免疫调节疗法正在研究中，以克服对ICI治疗的耐药性。包括toll样受体-9（TLR-9）和7/8（TLR-7/8）激动剂，干扰素基因刺激因子（STING）激动剂，和粪便微生物移植。在这次审查中,我们关注免疫治疗治疗黑色素瘤的最新进展,并对目前正在研究的新疗法进行了更新.
