4.6 Review Book Chapter

Immune Checkpoint Inhibitor Cardiotoxicity: Understanding Basic Mechanisms and Clinical Characteristics and Finding a Cure

Journal

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010919-023451

Keywords

immune checkpoint inhibitors; ICIs; cardio-oncology; cardio-immunology; immuno-oncology; myocarditis

Funding

  1. Howard Hughes Medical Institute
  2. US National Institutes of Health [R56 HL141466, R01 HL141466]

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ICIs alter the immune system's response to cancerous tissues but can lead to varying degrees of autoimmunity, with cardiovascular complications such as myocarditis emerging as significant side effects. Understanding the mechanisms underlying these toxicities may help improve patient outcomes by reducing treatment-related morbidity.
Immune checkpoint inhibitors (ICIs) attenuate mechanisms of self-tolerance in the immune system, enabling T cell responses to cancerous tissues and revolutionizing care for cancer patients. However, by lowering barriers against self-reactivity, ICIs often result in varying degrees of autoimmunity. Cardiovascular complications, particularly myocarditis but also arrhythmias, pericarditis, and vasculitis, have emerged as significant complications associated with ICIs. In this review, we examine the clinical aspects and basic science principles that underlie ICI-associated myocarditis and other cardiovascular toxicities. In addition, we discuss current therapeutic approaches. We believe a better mechanistic understanding of ICI-associated toxicities can lead to improved patient outcomes by reducing treatment-related morbidity.

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