A Systematic Review of the Mechanisms Involved in Immune Checkpoint Inhibitors Cardiotoxicity and Challenges to Improve Clinical Safety

Nestor Rubio-Infante, Yoel Adbel Ramírez-Flores, Elena Cristina Castillo, Omar Lozano, Gerardo García-Rivas, Guillermo Torre-Amione

Research output: Contribution to journalArticlepeer-review

Abstract

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block CTLA-4, PD-1, or PD-L1 and induce the activation of the immune system against cancer. Despite the efficacy of ICIs, which has improved the oncotherapy for patients with a variety of malignancies, several immune-related adverse events (irAEs) have been described, including those affecting the heart. Cardiac irAEs after ICI therapies, including myocarditis, can become life-threatening, and their pathogenic mechanisms remain unclear. Here, a systematic analysis was performed regarding the potential immune mechanisms underlying cardiac irAEs based on the immune adverse events induced by the ICIs: 1) recruitment of CD4+ and CD8+ T cells, 2) autoantibody-mediated cardiotoxicity, and 3) inflammatory cytokines. Furthermore, the impact of dual therapies in ICI-induced cardiac irAEs and the potential risk factors are reviewed. We propose that self-antigens released from cardiac tissues or cancer cells and the severity/advancement of cancer disease have an important role in ICI cardiotoxicity.

Original languageEnglish (US)
Article number851032
JournalFrontiers in Cell and Developmental Biology
Volume10
DOIs
StatePublished - Mar 30 2022

Keywords

  • CTLA-4
  • PD-1
  • cardiotoxicity
  • immune checkpoint inhibitors
  • myocarditis

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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