Autoimmune-related adverse events induced by immune checkpoint inhibitors

Abstract

Targeted immunotherapies, particularly immune checkpoint inhibitors (ICIs), have transformed cancer treatment by significantly improving patient response and survival rates. However, ICIs could disrupt self-tolerance, inducing the development of immune-related adverse events (irAEs). Most irAEs are classified as autoimmune conditions mediated by ICI-activated CD8+ cytotoxic T cells or activated B cells producing pathogenic autoantibodies. These irAEs phenotypically resemble spontaneous autoimmune disease and lead to considerable morbidity, health care costs, and compromised treatment efficacy. With the widespread use and new emergence of ICIs, the spectrum of ICI-induced irAEs has become increasingly extensive and complex. Concurrently, research in this field is advancing rapidly, a review summarizing the latest progress on irAEs is timely and essential. In this review, we highlight numerous recent research advances, covering the epidemiology, immune mechanisms, and diverse manifestations of irAEs, with a particular focus on organ-specific autoimmunity. We also discuss current strategies, challenges, and future directions for the prevention and therapeutic management of these adverse events.