免疫检查点抑制剂（ICI）治疗已经彻底改变了对多种癌症的治疗方式。ICI通过恢复T细胞功能来诱发抗癌免疫反应。然而，由此产生的免疫反应可能会产生非靶向效应，表现为约10-55％的患者出现自身免疫类型的严重免疫相关不良事件（irAE）。目前很难预测谁会出现irAE以及严重程度如何。鉴定高危严重irAE患者将彻底革命化患者护理。虽然irAE发展的病理机制仍不明确，但主机遗传因素被提出为这些事件的关键决定因素。本综述介绍了支持主机基因组在决定irAE风险方面作用的当前证据。 我们总结了ICI治疗后出现的irAE的光谱和时间，并描述了目前报道的与免疫调节因子在癌症免疫周期内表达、自身免疫疾病和irAE发生有关的生殖细胞系遗传变异。我们认为，主机免疫功能和自身免疫疾病的生殖细胞系遗传因素也可以解释irAE发展的风险。我们还支持对正在接受ICI治疗的患者进行全基因组关联研究，以识别可用于多基因风险评分以预测irAE风险的遗传变异。©2022年作者。

Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of various cancer types. ICIs reinstate T-cell function to elicit an anti-cancer immune response. The resulting immune response can however have off-target effects which manifest as autoimmune type serious immune-related adverse events (irAE) in ~10-55% of patients treated. It is currently challenging to predict both who will experience irAEs and to what severity. Identification of patients at high risk of serious irAE would revolutionise patient care. While the pathogenesis driving irAE development is still unclear, host genetic factors are proposed to be key determinants of these events. This review presents current evidence supporting the role of the host genome in determining risk of irAE. We summarise the spectrum and timing of irAEs following treatment with ICIs and describe currently reported germline genetic variation associated with expression of immuno-modulatory factors within the cancer immunity cycle, development of autoimmune disease and irAE occurrence. We propose that germline genetic determinants of host immune function and autoimmune diseases could also explain risk of irAE development. We also endorse genome-wide association studies of patients being treated with ICIs to identify genetic variants that can be used in polygenic risk scores to predict risk of irAE.© 2022. The Author(s).