Immune‐related adverse events after immune check point inhibitors: Understanding the intersection with autoimmunity

Abstract

SummaryImmune 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.