近年来，通过增强机体免疫系统对肿瘤细胞的杀伤作用，免疫检查点抑制剂（immune checkpoint inhibitor，ICI）在抗 肿瘤治疗中的应用获得了显著的临床疗效。然而，多项证据表明，免疫治疗在激活免疫系统的同时可导致独特的免疫相关不良 反应（immune-related adverse event，irAE），影响免疫治疗的疗效或需要中止治疗。近几年，随着 ICI 治疗临床试验的广泛开展， irAE 的发生情况、不良反应谱及其有效管理手段的开发越来越得到临床医生的关注。常见的 irAE 包括皮炎和甲状腺炎等，而 不同种类 ICI、不同治疗剂量或组合疗法，均可导致不同的 irAE 谱，同一 ICI 作用于不同肿瘤所致的不良反应谱亦有不同。目 前认为，irAE 的发生与机体自身免疫系统功能的改变相关，包括机体免疫系统过度激活、自身免疫耐受性的打破等，但其具体 机制仍不十分清楚。结合近年来在 ICI 治疗中 irAE 相关分子机制和预测标志物的关键理论和认识方面取得的诸多新进展，对 irAE 的发生特点和分子机制进行总结，并就其预测性标志物开发、irAE 管理原则改进和治疗新探索进行述评。

[Abstract] In recent years, immune checkpoint inhibitors (ICIs), by enhancing the killing effect of the human immune system on tumor cells, have obtained significant clinical efficacy in anti-tumor therapy. However, sufficient evidence has shown that immunotherapy can lead to unique immune-related adverse events (irAEs) when activating the immune system, which can affect the efficacy of immunotherapy or discontinue the treatment. In recent years, with the wide development of clinical trials of immunotherapy, more and more attention has been paid to the occurrence, adverse events profiles, as well as the development of effective management approaches of irAEs. Common irAEs include dermatitis and thyroiditis, etc. The use of different types of ICIs, different therapeutic doses or combination therapies can lead to different irAEs profiles, even the use of same ICI on different types of tumors can cause different irAEs profiles. At present, it is believed that the occurrence of irAEs is related to the changes of immune system, including excessive activation of the immune system and the breakdown of autoimmune tolerance, but the specific mechanism is still not very clear. This review integrated the new advances that have been made in recent years in the key theory and understanding of exploring the molecular mechanisms and predictive markers associated with irAEs of ICIs therapy to summarize the occurrence characteristics and molecular mechanisms of irAEs. This review also provide an overview of predictive markers, improvement on management principles, as well as new explorations for the treatment of irAEs

国家重点研发项目资助（No. 2016YFC1303800）；吉林省科技厅科技发展计划资助项目（No. 20190303146SF）；吉林省发展和改革委员会省级产业创新专项资金资助项目（No. 2017C022）；吉林省科技厅重点实验室建设项目资助（No. 20170622011JC）