To elucidate the cellular and molecular mechanisms underlying immune-related myocarditis (ICI-MC) induced by immune checkpoint inhibitors (ICIs), highlighting the significance of these mechanisms for improving patient outcomes.
Key Findings:
ICI-MC involves α-myosin-driven clonal expansion of cytotoxic CD8+ T cells and loss of regulatory T cell subsets, which may lead to increased myocardial damage.
Macrophage polarization towards M1 phenotypes is mediated via cGAS–STING and STAT1/NF-κB pathways, contributing to inflammation.
Crosstalk among various immune and stromal cells amplifies myocardial inflammation through chemokine and complement activation, indicating a complex interaction.
T-cell imbalance, particularly the expansion of terminally differentiated effector memory T cells, is a central driver of ICI-MC, suggesting targets for intervention.
Interpretation:
The review highlights the complex interplay of immune cells and pathways in the pathogenesis of ICI-MC, suggesting potential avenues for diagnosis and treatment that could significantly improve patient management.
Limitations:
The precise cellular and molecular mechanisms of ICI-MC remain incompletely defined, which may hinder therapeutic advancements.
The absence of sensitive biomarkers complicates diagnosis and management, emphasizing the need for further research.
Conclusion:
Future studies utilizing single-cell and multi-omics approaches are essential for refining diagnosis and developing cardioprotective interventions without compromising antitumor efficacy, necessitating collaboration across disciplines.
