Melanoma ranks as the fifth most common solid cancer in adults worldwide and is responsible for a significant proportion of skin-tumor-related deaths. The advent of immune checkpoint inhibition with anti-programmed death protein-1 (PD-1) antibodies has revolutionized the adjuvant treatment of high-risk, completely resected stage III/IV melanoma. However, not all patients benefit equally. Current strategies for improving outcomes involve adjuvant treatment in earlier disease stages (IIB/C) as well as perioperative treatment approaches. Interfering with T-cell exhaustion to counteract cancer immune evasion and the immunogenic nature of melanoma is key for anti-PD-1 effectiveness. Yet, the biological rationale for the efficacy of adjuvant treatment in clinically tumor-free patients remains to be fully elucidated. High-dose intermittent sun exposure (sunburn) is a well-known primary risk factor for melanomagenesis. Also, ultraviolet radiation (UVR)-induced immunosuppression may impair anti-cancer immune surveillance. In this review, we summarize the current knowledge about adjuvant anti-PD-1 blockade, including a characterization of the main cell types most likely responsible for its efficacy. In conclusion, we propose that local and systemic immunosuppression, to some extent UVR-mediated, can be restored by adjuvant anti-PD-1 therapy, consequently boosting anti-melanoma immune surveillance and the elimination of residual melanoma cell clones.
黑色素瘤在全球成人最常见实体肿瘤中位列第五，是皮肤肿瘤相关死亡的重要原因。抗程序性死亡蛋白-1（PD-1）抗体免疫检查点抑制疗法的出现，彻底改变了高风险、完全切除的III/IV期黑色素瘤的辅助治疗格局。然而，并非所有患者均能同等获益。当前改善预后的策略包括在更早期疾病阶段（IIB/C期）进行辅助治疗，以及围手术期治疗方案。干扰T细胞耗竭以对抗癌症免疫逃逸及黑色素瘤的免疫原性，是抗PD-1疗法发挥疗效的关键。但辅助治疗在临床无瘤患者中有效的生物学机制仍有待充分阐明。高强度间歇性日光暴露（晒伤）是公认的黑色素瘤发生主要风险因素。此外，紫外线辐射诱导的免疫抑制可能损害抗癌免疫监视功能。本综述总结了当前关于辅助性抗PD-1阻断治疗的认知，包括对其疗效主要作用细胞类型的特征分析。最后我们提出，辅助性抗PD-1治疗可在一定程度上恢复由紫外线辐射介导的局部及全身免疫抑制，从而增强抗黑色素瘤免疫监视功能并清除残留黑色素瘤细胞克隆。
肿瘤(癌症)患者之家