Cardiac myosin-specific autoimmune T cells contribute to immune-checkpoint-inhibitor-associated myocarditis

Cell Rep. 2022 Nov 8;41(6):111611. doi: 10.1016/j.celrep.2022.111611.


Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear. Here, we show the development of myocarditis in A/J mice induced by anti-PD-1 monoclonal antibody (mAb) administration alone without tumor cell inoculation, immunization, or viral infection. Mice with myocarditis have increased cardiac infiltration, elevated cardiac troponin levels, and arrhythmia. Anti-PD-1 mAb treatment also causes irAEs in other organs. Autoimmune T cells recognizing cardiac myosin are activated and increased in mice with myocarditis. Notably, cardiac myosin-specific T cells are present in naive mice, showing a phenotype of antigen-experienced T cells. Collectively, we establish a clinically relevant mouse model for ICI-associated myocarditis and find a contribution of cardiac myosin-specific T cells to ICI-associated myocarditis development and pathogenesis.

Keywords: CP: Immunology; ICI; ICI-associated myocarditis; PD-1; autoimmune T cells; cardiac myosin; immune checkpoint inhibitor.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological*
  • Autoimmunity
  • Cardiac Myosins
  • Immune Checkpoint Inhibitors
  • Mice
  • Myocarditis* / chemically induced
  • Myocarditis* / pathology
  • T-Lymphocytes / pathology


  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • Cardiac Myosins
  • Immune Checkpoint Inhibitors