From tumor immunotherapy to myocardial injury: A mechanistic discussion of immune checkpoint inhibitor‑related myocarditis (Review).

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, markedly improving the survival rate of numerous malignancies. However, the emergence of immune‑related adverse events, particularly ICI‑related myocarditis, poses substantial clinical challenges. Despite its relatively low incidence, ICI‑related myocarditis demands urgent attention due to high mortality rates and treatment‑related cardiovascular toxicity. The present review provides an in‑depth analysis of the immunopathological mechanisms of ICI‑related myocarditis, with a focus on the physiological role of immune checkpoints, the core mechanisms of immune tolerance failure following ICI blockade, the influence of genetics and the microenvironment, and the effects of myocardial electrophysiology and hormones. Attention is also given to the cellular and molecular mechanisms, particularly the roles of T cells and macrophages. The current review highlights the critical interactions between these factors in the initiation and progression of ICI‑related myocarditis. In addition, clinical manifestations, diagnostic criteria incorporating advanced imaging and biomarker profiling, and differential diagnosis considerations are summarized, underscoring the necessity of multidisciplinary collaboration for timely intervention. Mechanistic elucidation of ICI‑related myocarditis will enable preventive strategies, optimized early diagnostics and improved patient outcomes, and may ultimately reduce the clinical incidence of this disease.