Exosomes and Extracellular Vesicles in CAR-T Cell Therapy: Emerging Mediators and Biomarkers of Cardiac Injury.

Chimeric antigen receptor T-cell (CAR-T) therapy has transformed outcomes in hematologic malignancies but is frequently complicated by cardiovascular toxicity, most notably in the setting of cytokine release syndrome. While systemic inflammation, endothelial activation, and myocardial stress have been implicated, the mechanistic links between immune activation and cardiac injury remain incompletely understood. Exosomes and other extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication during immune responses, carrying bioactive cargo including cytokines, microRNAs, proteins, and lipids that can modulate cardiovascular function. In the context of CAR-T therapy, EVs derived from activated T-cells, tumor cells, and injured endothelium may amplify inflammatory signaling, promote endothelial dysfunction, and contribute directly to myocardial injury. Importantly, EVs are detectable in peripheral blood and exhibit dynamic changes in concentration and cargo during CAR-T-associated toxicities, positioning them as promising biomarkers for early detection, risk stratification, and prognostication of cardiac injury. This review synthesizes current evidence on the biogenesis, functional roles, and cardiovascular effects of exosomes and EVs in CAR-T therapy, highlighting their potential as mechanistic mediators and translational biomarkers. We also discuss existing knowledge gaps, technical challenges in EV characterization, and future directions for integrating EV-based diagnostics into cardio-oncology practice.