PD-1/PD-L1抑制剂在黑色素瘤治疗中的研究进展

Research Advances in PD-1/PD-L1 Inhibitors for Melanoma Therapeutics

摘要: 黑色素瘤是一种由黑色素细胞引起的高肿瘤突变负荷(tumor mutation burden, TMB)，高侵袭性且易转移的恶性肿瘤，且病因复杂，紫外线是主要危险因素。程序性死亡受体1 (programmed death-1, PD-1)/程序性死亡配体1 (programmed death-ligand 1, PD-L1)是调节免疫反应的免疫检查点，二者结合后，抑制T细胞增殖和活性，导致肿瘤微环境中T细胞耗竭，促进肿瘤的免疫逃逸。免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)，特别是以PD-1/PD-L1为靶点的单抗类抑制剂的应用彻底改变了黑色素瘤的治疗格局，显著改善患者预后。PD-1/PD-L1单抗药物与其他药物的联合用药有望进一步提高黑色素瘤患者的生存率。本文对黑色素瘤的流行病学和发病机制进行了回顾，总结了PD-1/PD-L1抑制剂当前的研究现状，重点讨论了已上市的PD-1/PD-L1单抗临床疗效和联合用药方案，为药物的开发和合理的临床联合治疗策略提供参考。

Abstract: Melanoma is a highly malignant tumor characterized by a high tumor mutation burden (TMB) caused by melanocytes; it is highly invasive and prone to metastasis. Its etiology is complex, with ultraviolet radiation being a primary risk factor. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) are immune checkpoints regulating immune responses. Their binding inhibits T-cell proliferation and activity, leading to T-cell exhaustion in the tumor microenvironment and promoting tumor immune escape. Immune checkpoint inhibitors (ICIs), particularly monoclonal antibody inhibitors targeting PD-1/PD-L1, have revolutionized melanoma treatment, significantly improving patient outcomes. Combination therapy with PD-1/PD-L1 monoclonal antibodies and other agents holds promise for further enhancing survival rates in melanoma patients. This review examines the epidemiology and pathogenesis of melanoma, summarizes the current research status of PD-1/PD-L1 inhibitors, and focuses on the clinical efficacy of marketed PD-1/PD-L1 monoclonal antibodies and combination regimens. It aims to provide insights for drug development and rational clinical combination therapy strategies.