Cardiovascular toxicity from immune checkpoint inhibitor therapy: an inflammatory continuum

Area of Science:

• Cardiovascular Medicine
• Immunology
• Oncology

Background:

• Immune checkpoint inhibitor (ICI) therapy offers significant benefits for advanced cancers.
• However, ICIs are associated with a range of cardiovascular immune-related adverse events (irAEs).
• Myocarditis is a severe manifestation, alongside left ventricular dysfunction and vascular inflammation.

Purpose of the Study:

• To review the mechanisms underlying ICI-related cardiovascular toxicity.
• To describe the clinical manifestations of these adverse events.
• To discuss the challenges in managing cardiac safety during ICI therapy.

Main Methods:

• Review of current evidence on ICI cardiovascular toxicity.
• Analysis of immunological mechanisms.
• Discussion of clinical presentations and management strategies.

Main Results:

• ICI therapy disrupts cardiac immune tolerance, leading to T-cell and macrophage-mediated myocardial injury.
• Checkpoint inhibition can expand autoreactive T-cells targeting cardiac autoantigens like α-myosin.
• ICI-related inflammation also contributes to endothelial dysfunction and accelerated atherosclerosis.
• Mitochondrial damage and cellular stress pathways link to innate immune signaling in the heart.

Conclusions:

• ICI-related cardiovascular toxicity involves complex immune dysregulation affecting the heart and vasculature.
• Early detection via biomarkers and imaging, alongside immunomodulation, may improve outcomes.
• Balancing anti-cancer efficacy with cardiac safety presents a significant clinical challenge.