Immunotherapy-associated Cardiotoxicity: a Comprehensive Review of Checkpoint inhibitors, monoclonal, cellular, and cytokine-based Treatments.

Abstract

Opinion statement: Immunotherapy has revolutionized cancer treatment and dramatically improved outcomes across a broad range of malignancies. However, the expanding use of immune checkpoint inhibitors, monoclonal antibodies, Chimeric Antigen Receptor (CAR)-T cell therapies, bispecific T cell engagers, cytokines, and other immunotherapeutic approaches has brought forward a new spectrum of immune-related adverse events, among which cardiotoxicities-though relatively uncommon-are increasingly recognized as clinically significant and potentially life-threatening. These events range from fulminant myocarditis and arrhythmias to non-inflammatory left ventricular dysfunction, pericardial syndromes, and vascular inflammation, and often present diagnostic and management challenges due to their variable timing, severity, and underlying mechanisms. While immune checkpoint inhibitors remain the most studied in terms of cardiovascular toxicity, emerging evidence suggests that other modalities-including adoptive cell therapies and cytokine-based agents-also carry substantial cardiovascular risk, particularly through cytokine release syndrome, endothelial injury, or metabolic disruption. Understanding the pathophysiological mechanisms of these toxicities, including T-cell-mediated inflammation, mitochondrial dysfunction, and immune checkpoint dysregulation in the heart, is essential for early recognition and effective mitigation. As immunotherapies continue to expand in clinical use and combination regimens become more complex, there is a critical need for interdisciplinary cardio-oncology approaches that integrate cardiovascular risk assessment, monitoring, and tailored management strategies. Moving forward, identifying predictive biomarkers, optimizing surveillance protocols, and elucidating shared and therapy-specific mechanisms will be key to minimizing harm while preserving the oncologic efficacy of these transformative therapies.