免疫检查点抑制剂（ICIs）已经彻底改变了癌症治疗。然而，其使用常常与可能影响任何器官的免疫相关不良事件（irAEs）相关。介导此类irAEs的机制仍然不了解，目前也缺乏预测irAEs发生的生物标志物。越来越多的证据显示在ICIs治疗期间介导irAEs的自身抗原的重要性，尤其是在黑色素瘤患者中已经描述清楚的黑素细胞分化抗原。本综述将重点讨论在免疫疗法治疗的非小细胞肺癌患者中介导自身免疫性皮肤毒性和肺炎的两类新型自身抗原。这些自身抗原特异性T细胞被认为不仅介导irAEs，同时也介导抗肿瘤反应，因此与自身免疫毒性和ICI治疗反应相关。我们进一步讨论了irAEs的新兴细胞和蛋白质组学免疫标记，它们可能作为生物标志物帮助预测哪些患者更容易发生这些irAEs。发现与ICI治疗有关的新肿瘤抗原，并确定相关生物标志物，将使我们在了解ICIs的机制方面取得进展，并有助于监测更容易发生irAEs的患者。最后，我们讨论了收集ICI相关机制研究样本的当前挑战以及在鉴别反应和irAEs的免疫标记之间的困难。《免疫学评论》©2023由John Wiley & Sons Ltd出版。

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, their use is frequently associated with immune-related adverse events (irAEs) potentially affecting any organ. The mechanisms mediating such irAEs remain poorly understood and biomarkers to predict the development of irAEs are lacking. Growing evidence shows the importance of self-antigens in mediating irAEs during ICI therapy, in particular the well-described melanocyte differentiation antigens in melanoma patients. This review will focus on two novel classes of self-antigens involved in mediating autoimmune skin toxicity and pneumonitis in non-small cell lung cancer patients treated with immunotherapy. T cells specific for these self-antigens are thought to not only mediate irAEs but are thought to simultaneously mediate anti-tumor responses and are therefore associated with both autoimmune toxicity and response to ICI therapy. We further discuss emerging cellular and proteomic immune signatures of irAEs that may serve as biomarkers to help predict which patients are at higher risk of developing these irAEs. The determination of new tumor antigens involved in ICI therapy and the identification of related biomarkers brings us a step forward in the mechanistic understanding of ICIs and will help to monitor patients at higher risk of developing irAEs. Lastly, we discuss the current challenges in collecting research samples for the study of ICI-related mechanisms and in distinguishing between immune signatures of response and those of irAEs.Immunological Reviews© 2023 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.