Immune-related adverse events after immune check point inhibitors: Understanding the intersection with autoimmunity.
Immune-related adverse events after immune check point inhibitors: Understanding the intersection with autoimmunity.
复制标题
免疫检查点抑制剂后的免疫相关不良事件：了解与自身免疫的交叉点。
DOI：
10.1111/imr.13247
复制
发表时间：
2023
影响因子：
8.7
通讯作者：
Buckner,JaneH
中科院分区：
文献类型：
--
作者：
Singh,Namrata;Hocking,AnneM;Buckner,JaneH
免疫检查点抑制剂疗法通过阻断参与调节T细胞的抑制性分子起作用，从而释放肿瘤特异性T细胞以破坏其肿瘤靶标。然而，免疫检查点抑制剂（ICI）也可能导致自身耐受性破坏，导致免疫相关不良事件（irAE），包括组织特异性自身免疫。本综述讨论了驱动ICI诱导的irAE的机制是否与驱动自发性自身免疫的机制相同或不同的问题，重点关注ICI诱导的糖尿病、ICI诱导的关节炎和ICI诱导的甲状腺炎，因为对1型糖尿病、类风湿性关节炎和桥本甲状腺炎中自身免疫的发展有丰富的了解。它回顾了关于遗传学和自身抗体在ICI诱导的irAE发展中作用的现有知识，并介绍了利用单细胞组学方法鉴定与ICI诱导的irAE相关的T细胞特征的新研究。总的来说，这些研究表明ICI诱导的irAE和自身免疫性疾病之间存在相似性和差异，并且平行研究它们将为维持免疫耐受的关键机制提供重要见解。
Immune checkpoint inhibitor therapies act through blockade of inhibitory molecules involved in the regulation of T cells, thus releasing tumor specific T cells to destroy their tumor targets. However, immune checkpoint inhibitors (ICI) can also lead to a breach in self‐tolerance resulting in immune‐related adverse events (irAEs) that include tissue‐specific autoimmunity. This review addresses the question of whether the mechanisms that drive ICI‐induced irAEs are shared or distinct with those driving spontaneous autoimmunity, focusing on ICI‐induced diabetes, ICI‐induced arthritis, and ICI‐induced thyroiditis due to the wealth of knowledge about the development of autoimmunity in type 1 diabetes, rheumatoid arthritis, and Hashimoto's thyroiditis. It reviews current knowledge about role of genetics and autoantibodies in the development of ICI‐induced irAEs and presents new studies utilizing single‐cell omics approaches to identify T‐cell signatures associated with ICI‐induced irAEs. Collectively, these studies indicate that there are similarities and differences between ICI‐induced irAEs and autoimmune disease and that studying them in parallel will provide important insight into the mechanisms critical for maintaining immune tolerance.