免疫检查点抑制剂（ICIs）是潜在拯救生命的癌症治疗方法，可能会引发免疫相关的不良事件（irAEs）。irAEs可以影响任何器官，并且在表现上从轻度副作用到危及生命的并发症都有所不同。irAEs与抗肿瘤免疫反应之间的关系复杂多样，可能取决于irAEs的发生器官、肿瘤组织学和患者。虽然一些irAEs可能代表了对肿瘤细胞和健康组织之间共有的抗原的免疫反应，但其他irAEs可能与抗肿瘤免疫反应无关。临床观察表明，轻度irAEs与ICIs的反应呈正相关，但重度irAEs与临床益处之间的相关性不太明确。目前，重度irAEs通常通过中断或永久停止ICI治疗，并给予经验选择的全身免疫抑制药物治疗。然而，这些干预可能会降低ICIs的抗肿瘤效果。为了理解irAEs与肿瘤微环境之间的机制关系，我们获得了有意义的见解，并提出了治疗irAEs的治疗靶点，这些靶点可能能维持甚至增强ICI的疗效。我们探讨了irAEs与抗肿瘤免疫的临床和分子关系，以及irAE治疗在塑造抗肿瘤免疫反应中的作用。© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immune checkpoint inhibitors (ICIs) are potentially life-saving cancer therapies that can trigger immune-related adverse events (irAEs). irAEs can impact any organ and range in their presentation from mild side effects to life-threatening complications. The relationship between irAEs and antitumor immune responses is nuanced and may depend on the irAE organ, the tumor histology, and the patient. While some irAEs likely represent an immune response against antigens shared between tumor cells and healthy tissues, other irAEs may be entirely unrelated to antitumor immune responses. Clinical observations suggest that low-grade irAEs have a positive association with responses to ICIs, but the correlation between severe irAEs and clinical benefit is less clear. Currently, severe irAEs are typically treated by interrupting or permanently discontinuing ICI treatment and administering empirically selected systemic immunosuppressive agents. However, these interventions could potentially diminish the antitumor effects of ICIs. Efforts to understand the mechanistic relationship between irAEs and the tumor microenvironment have yielded meaningful insights and nominated therapeutic targets for irAE management that may preserve or even boost ICI efficacy. We explore the clinical and molecular relationship between irAEs and antitumor immunity as well as the role that irAE treatments may play in shaping antitumor immune responses.© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.