Mechanisms of Cardiovascular Toxicities Associated With Immunotherapies

Circ Res. 2021 May 28;128(11):1780-1801. doi: 10.1161/CIRCRESAHA.120.315894. Epub 2021 May 3.

Abstract

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.

Keywords: cardiotoxicity; cytokine release syndrome; cytokine storm; immune checkpoint inhibitors; immunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Bispecific / adverse effects
  • Antibodies, Bispecific / therapeutic use
  • Cardiotoxicity / immunology
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / immunology
  • Cytokine Release Syndrome / complications
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / therapy
  • Disease Models, Animal
  • Dogs
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / adverse effects*
  • Immunotherapy / methods
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods
  • Lymphocyte Activation
  • Mice
  • Neoplasms / therapy*
  • Rats
  • Receptors, Chimeric Antigen
  • T-Lymphocytes / transplantation

Substances

  • Antibodies, Bispecific
  • Immune Checkpoint Inhibitors
  • Receptors, Chimeric Antigen