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

Authors

• Taejoon Won, Johns Hopkins University School of Medicine
• Hannah M. Kalinoski, Johns Hopkins University Bloomberg School of Public Health
• Megan K. Wood, Johns Hopkins University Bloomberg School of Public Health
• David M. Hughes, Johns Hopkins University Whiting School of Engineering
• Camille M. Jaime, Johns Hopkins University School of Medicine
• Paul Delgado, Johns Hopkins University Bloomberg School of Public Health
• Monica V. Talor, Johns Hopkins University School of Medicine
• Ninaad Lasrado, University of Nebraska-Lincoln, Harvard Medical School
• Jay Reddy, University of Nebraska-LincolnFollow
• Daniela Čiháková, Johns Hopkins University School of Medicine

Document Type

Article

Date of this Version

11-8-2022

Citation

Won et al., 2022, Cell Reports 41, 111611 November 8, 2022. https://doi.org/10.1016/j.celrep.2022.111611

Comments

Open access.

Abstract

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.