Immune checkpoint inhibitor-associated myocarditis: clinical and mechanistic insights.

BACKGROUND

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can cause immune-related adverse events, including potentially severe cardiovascular toxicities. Although rare, immune checkpoint inhibitor-associated myocarditis (ICIM) can present early and may be rapidly fatal, posing a significant challenge at the crossroads of oncology, immunology, and cardiology.

PURPOSE: This review synthesizes emerging clinical and experimental evidence to refine understanding of risk factors for immune checkpoint inhibitor-associated myocarditis and to outline a practical clinic-to-bench framework linking surveillance and diagnostic decision-making to pathogenic cellular programs.

CONCLUSIONS

We highlight the cardiac immune microenvironment as a network of multicellular interactions in which cytotoxic T cells and inflammatory myeloid subsets engage with cardiomyocytes, endothelial cells, and fibroblasts through reinforcing feedback loops. Specifically, interferon-γ (IFN-γ)-driven myeloid activation and chemokine programs (CXCR3-CXCL9/10, CXCL16-CXCR6) coordinate immune cell trafficking and promote tissue injury, while stress-related cell death pathways can trigger innate immune sensing via the cGAS-STING axis. Current management remains centered on early recognition and corticosteroid-based immunosuppression, but emerging mechanistic insights reveal opportunities to improve therapy by targeting immune cell trafficking and inflammatory amplification pathways. Together, these advances support a more integrated cardio-oncology approach to ICIM, in which mechanistic insights inform risk stratification, earlier diagnosis, and the development of more precise immunomodulatory therapies.