4.7 Review

Mechanisms of Cardiovascular Toxicities Associated With Immunotherapies

Journal

CIRCULATION RESEARCH
Volume 128, Issue 11, Pages 1780-1801

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.120.315894

Keywords

cardiotoxicity; cytokine release syndrome; cytokine storm; immune checkpoint inhibitors; immunology

Funding

  1. NIH [T32 HL007731-28]
  2. BMS
  3. Incyte
  4. Celgene/BMS
  5. Janssen
  6. Bluebird Bio
  7. Sutro Biopharma
  8. Teneobio
  9. Poseida
  10. Nektar
  11. Array/Pfizer
  12. Oncosec
  13. Parker Institute for Cancer Immunotherapy
  14. Regeneron
  15. Replimune
  16. National Institutes of Health [R01HL141466, R01HL155990, R01HL156021]

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Immune-based therapies have transformed cancer treatments, but cardiovascular complications arising from these therapies present new challenges in cardio-oncology. Understanding the mechanisms of immune activation and associated cardiovascular toxicities is crucial for addressing the cardiovascular sequelae of immunotherapy.
Immune-based therapies have revolutionized cancer treatments. Cardiovascular sequelae from these treatments, however, have emerged as critical complications, representing new challenges in cardio-oncology. Immune therapies include a broad range of novel drugs, from antibodies and other biologics, including immune checkpoint inhibitors and bispecific T-cell engagers, to cell-based therapies, such as chimeric-antigen receptor T-cell therapies. The recognition of immunotherapy-associated cardiovascular side effects has also catapulted new research questions revolving around the interactions between the immune and cardiovascular systems, and the signaling cascades affected by T cell activation, cytokine release, and immune system dysregulation. Here, we review the specific mechanisms of immune activation from immunotherapies and the resulting cardiovascular toxicities associated with immune activation and excess cytokine production.

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