한빛사논문
- 조회787
Taejoon Won1, Hannah M. Kalinoski2, Megan K. Wood2, David M. Hughes3, Camille M. Jaime4, Paul Delgado2, Monica V. Talor1, Ninaad Lasrado5,6, Jay Reddy5, Daniela Čiháková1,2,7
1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
3Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA
4Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
6Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
7Lead contact
Corresponding author: Daniela Čiháková
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.
논문정보
- Research article
- 2022년 11월 (BRIC 등록일 2023-01-17)
- 국외 연구진
관련 웨비나
![자가면역 T 세포와 심근염 [Cell Reports.]](/upload/board/files/onseminar/thumb/thumb_0000515.png)
학술웨비나
자가면역 T 세포와 심근염 [Cell Reports.] Immune checkpoint inhibitor (ICI)는 효과적인 암 치료제이나, 부작용으로서 자가면역성 염증 질환을 유발한다. 심근염은 ICI 투여 후 발생하는 부작용 중 하나이며 높은 사망률을 보인다. 하지만, 현재까지 ICI-연관 심근염 (ICI-associated myocarditis)의 발생기전은 명확하지 않다. 이번 연구에서 우리는 ICI-연관 심근염 마우스 모델을 직접 개발하였고, 심장은 포함한 다양한 장기에서 자가면역성 염증이 발생한 것을 확인하였다. 심근염을 가진 마우스에서는 심장 항원 중 하나인 cardiac myosin을 인식하는 자가면역 T 세포가 활성화되었고 그 수가 증가하였다. 우리는 건강한 마우스의 심장에서도 자가면역 T 세포를 발견하였다. 따라서, ICI 투여는 심장 항원을 인식하는 자가면역 T 세포를 활성화하여 심근염을 유발하는 것으로 보인다. immune checkpoint inhibitor, 심근염, 자가면역 T 세포- 원태준(Johns Hopkins University School of Medicine)
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