With immune checkpoint inhibitors (ICIs) becoming the mainstay of treatment for many cancers, managing their immune-related adverse events (irAEs) has become an important part of oncological care. This Review covers the clinical presentation of irAEs and crucial aspects of reversibility, fatality and long-term sequelae, with special attention to irAEs in specific patient populations, such as those with autoimmune diseases. In addition, the genetic basis of irAEs, along with cellular and humoral responses to ICI therapy, are discussed. Detrimental effects of empirically used high-dose steroids and second-line immunosuppression, including impaired ICI effectiveness, call for more tailored irAE-treatment strategies. We discuss open therapeutic challenges and propose potential avenues to accelerate personalized management strategies and optimize outcomes.
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