心肌炎
病毒性心肌炎
免疫系统
医学
免疫学
单克隆抗体
肌球蛋白
抗体
内科学
生物
细胞生物学
作者
Tae Joon Won,Hannah M. Kalinoski,Megan Kay Wood,David Hughes,Camille M. Jaime,Paul Delgado,Monica V. Talor,Ninaad Lasrado,Jay Reddy,Daniela Čiháková
出处
期刊:Cell Reports
[Elsevier]
日期:2022-11-01
卷期号:41 (6): 111611-111611
被引量:28
标识
DOI:10.1016/j.celrep.2022.111611
摘要
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.
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