Understanding immune checkpoint inhibitors-related myocarditis: Mechanisms and targeted therapeutic pathways

Immune checkpoint inhibitor (ICI)-related myocarditis is a rare but often fatal adverse event that has gained increasing attention due to the widespread clinical use of ICIs. This review explores the development of immune cells and their critical roles in cardiac autoimmunity, with particular focus on defects in central tolerance, the role of immune checkpoints, T cell trafficking to the heart, and the involvement of resident cardiac macrophages. It also introduces the key pathogenic mechanisms of ICI-related myocarditis, including the activation of autoreactive T cells that recognize self or shared antigens, the crosstalk between T cells and macrophages, and macrophage polarization. In addition, we also discuss current and emerging targetable therapeutic pathways, including cytokine modulation, the JAK/STAT pathway, and the use of CTLA-4 immunoglobulin. We further summarize practical diagnostic and prognostic approaches, including the role and limitations of troponin-based monitoring, echocardiography, magnetic resonance imaging, PET-CT applications, and endomyocardial biopsy. This review aims to establish a mechanistic framework that integrates pathogenic mechanisms, diagnostic and prognostic approaches, and therapeutically targetable pathways in ICI-related myocarditis.