Immune Responses in Checkpoint Inhibitor-Associated Cardiovascular Immune-Related Adverse Events: JACC: CardioOncology State-of-the-Art Review

Although immune checkpoint inhibitors have improved cancer outcomes, their use can trigger autoimmune toxicities affecting essentially any organ system. In the cardiovascular system, these immune-related adverse events can manifest as myocarditis, pericarditis, accelerated atherosclerosis, vasculitis, arrhythmias, and other conditions. These cardiovascular toxicities are driven by the loss of peripheral tolerance, but the underlying mechanisms remain incompletely understood. Recent murine and human studies, particularly in immune checkpoint inhibitor-associated atherosclerosis and myocarditis, have begun to reveal the cellular and molecular mediators. Disinhibited T cell function is a central driver, but other immune and nonimmune cell types have also been implicated. Multiple inflammatory and chemokine receptor signaling pathways are activated, offering potential targets for intervention. The growing mechanistic understanding of these cardiovascular toxicities has begun to inform new diagnostic and therapeutic strategies, though additional prospective trials are needed.