Cardio- immunotoxicity of Immune Checkpoint Inhibitors: A Focus on Myocarditis

Abstract

Immune checkpoint inhibitors (ICIs) have changed modern oncology by considerably improving survival outcomes across a wide range of cancers by boosting antitumor immune responses. In cancers like melanoma, lung cancer, renal cell carcinoma, and Hodgkin lymphoma, agents that target cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1) have shown impressive efficiency. However, immune-related adverse events (irAEs), among which myocarditis is one of the rarest but deadliest toxicities, can be brought on by the immune system's nonspecific activation. Immune-mediated myocardial inflammation brought on by loss of self-tolerance, excessive T-cell activation, cytokine dysregulation, and cross-reactivity between tumor and cardiac antigens are the hallmarks of ICI-associated myocarditis. Due to the condition's quick progression to arrhythmias, cardiogenic shock, and fulminant heart failure, it has a high death rate despite its low incidence. The risk of cardiotoxicity is further increased by concurrent autoimmune disorders, pre-existing cardiovascular disease, and combination immunotherapy. With a focus on immunopathogenesis, molecular mechanisms, inflammatory signaling pathways, histopathological findings, biomarkers, and diagnostic modalities, this review investigates the toxicological foundation of ICI-associated myocarditis. Additionally, new developments in translational cardio-oncology are emphasized to enhance early detection and lower mortality. In order to balance therapeutic efficacy with cardiovascular safety in cancer patients receiving immunotherapy, it is crucial to comprehend the cardioimmunotoxic processes underpinning checkpoint blockade therapy.