Fan Yong, Geng Yan, Shen Lin, Zhang Zhuoli
Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, 100034, China.
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Front Med. 2021 Feb;15(1):33-42. doi: 10.1007/s11684-019-0735-3. Epub 2020 Aug 10.
Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.
免疫疗法最近在癌症治疗领域引发了一场范式转变，其中免疫检查点抑制剂（ICIs）是被批准用于多种晚期恶性肿瘤的最成功药物。然而，鉴于效应T细胞非特异性激活的性质，ICIs几乎与所有器官或系统中发生免疫相关不良事件（irAEs）的重大风险显著相关。接受ICIs联合治疗的患者中，高达90%经历了irAEs，其中大多数为低级别毒性。细胞毒性淋巴细胞抗原-4和程序性细胞死亡蛋白-1/程序性细胞死亡配体1抑制剂通常表现出不同的irAEs特征。在本综述中，描述了ICIs的作用机制以及它们可能导致irAEs的方式。然而，一些尚未解决的挑战，实际上是引人入胜的问题，如irAEs与癌症治疗反应之间的关联、肿瘤对irAEs治疗的反应以及挑战性人群中的ICIs，都进行了全面总结。
