As the understanding of immune-related mechanisms in the development and progression of cancer advances, immunotherapies, notably Immune Checkpoint Inhibitors (ICIs), have become integral in comprehensive cancer treatment strategies. ICIs reactivate T-cell cytotoxicity against tumors by blocking immune suppressive signals on T cells, such as Programmed Death-1 (PD-1) and Cytotoxic T-lymphocyte Antigen-4 (CTLA-4). Despite their beneficial effects, ICIs are associated with immune-related adverse events (irAEs), manifesting as autoimmune side effects across various organ systems. A particularly alarming irAE is life-threatening myocarditis. This rare but severe side effect of ICIs leads to significant long-term cardiac complications, including arrhythmias and heart failure, and has been observed to have a mortality rate of up to 50% in affected patients. This greatly limits the clinical application of ICI-based immunotherapy. In this review, we provide a comprehensive summary of the current knowledge regarding the diagnosis and management of ICI-related myocarditis. We also discuss the utility of preclinical mouse models in understanding and addressing this critical challenge.
Keywords: Immune checkpoint inhibitors; Immunotherapy toxicity; Immunotherapy-related adverse reactions; Myocarditis.
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