The Evolving Landscape of Immunotoxicity: Charting Mechanisms and Future Strategies for Immune Checkpoint Inhibitor Adverse Events

ABSTRACT The use of immune checkpoint inhibitors (ICIs) has significantly improved the efficacy of cancer therapy, but their associated immune‐related adverse events (irAEs) can severely compromise treatment safety. This review systematically summarizes the core mechanisms underlying irAEs, which include multi‐organ damage resulting from T‐cell dysfunction, B‐cell‐mediated autoantibody abnormalities, cytokine network dysregulation, and monocyte‐driven inflammatory cascades. Identified risk factors encompass a range of elements, including host clinical characteristics and underlying diseases, gut microbiota dysbiosis, characteristics of the treatment regimen, tumor type and its histological features, genetic factors and immunogenetic polymorphisms, pre‐existing autoimmune conditions or a history of autoimmunity, and a history of previous exposures alongside various environmental factors. The grading criteria, their clinical context and incidence rates, and clinical management strategies for irAEs affecting various organ systems are detailed herein. Future research should aim to deeply analyze the shared mechanisms and temporal dynamics between irAEs and anti‐tumor effects, develop targeted irAE prediction and monitoring systems, and optimize strategies for irAE prevention and treatment.