Advances in molecular mechanisms of immune checkpoint inhibitor-associated myocarditis

Immune checkpoint inhibitors (ICIs) are regarded as the most widely used immunotherapy for malignancies, which mainly includes inhibitors of cytotoxic T lymphocyte associated antigen-4 (CTLA-4), programmed death protein-1/ligand-1 (PD-1/PD-L1) and lymphocyte activation gene-3 (LAG-3). One of the most fatal immune-related adverse events (irAE) resulted from ICIs is immune checkpoint inhibitor-associated myocarditis (ICIAM). The incidence of ICIAM in combination therapy is much higher than that of monotherapy. The molecular mechanisms of ICIAM mainly include immune checkpoints as neoantigens, heterotopic recognition of tumor homologous antigens, blocking the cardioprotective effect of immune checkpoints, generation of autoantibodies or inflammatory cytokines and abnormal regulation of microbial. There are several pharmacological and non-pharmacological regiments for the treatment of ICIAM. Multi-disciplinary efforts are still needed to explore the molecular mechanisms of ICIAM and to improve the treatment managements.