Immune checkpoint inhibitor–associated myocarditis: manifestations and mechanisms
Open accessAbstract
Immune checkpoint inhibitors (ICIs) have transformed the treatment of various cancers, including malignancies once considered untreatable. These agents, however, are associated with inflammation and tissue damage in multiple organs. Myocarditis has emerged as a serious ICI-associated toxicity, because, while seemingly infrequent, it is often fulminant and lethal. The underlying basis of ICI-associated myocarditis is not completely understood. While the importance of T cells is clear, the inciting antigens, why they are recognized, and the mechanisms leading to cardiac cell injury remain poorly characterized. These issues underscore the need for basic and clinical studies to define pathogenesis, identify predictive biomarkers, improve diagnostic strategies, and develop effective treatments. An improved understanding of ICI-associated myocarditis will provide insights into the equilibrium between the immune and cardiovascular systems.
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The discovery of α-MyHC-specific T cells in ICI myocarditis suggests potential involvement of autoreactive T cells targeting α-MyHC in the initiation and progression of other forms of myocarditis.
“This discovery suggests a potential involvement of autoreactive T cells targeting α -MyHC in the initiation and progression of other forms of myocarditis.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [44]
The “Mechanisms of ICI-associated myocarditis” section describes α-myosin-heavy-chain–reactive T cells in a model of autoimmune myocarditis, supporting their potential relevance to other forms of myocarditis. But it identifies the antigens that elicit T-cell responses in ICI-associated myocarditis as an open question; it does not report the claimed discovery of α-MyHC-specific T cells in ICI myocarditis. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRecent cases of ICI myocarditis have expanded insights into the role of α-MyHC-specific T cells in myocarditis development.
“Recent cases of ICI myocarditis have expanded our insights into the role of α -MyHC-specific T cells in myocarditis development. 41-46”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [44]
The Mechanisms of ICI-associated myocarditis section describes α-myosin-heavy-chain-reactive T cells in a mouse model of autoimmune myocarditis. It explicitly says that mechanism had not yet been explored in ICI-associated myocarditis and identifies the antigens driving ICI-associated T-cell responses as an open question. The paper therefore supports a role for these T cells in myocarditis generally, but not the claimed insight from recent ICI myocarditis cases. (LLM, conf=0.85)
Experimental — accuracy not yet measuredICI myocarditis is an infrequent but potentially fatal condition associated with ICI therapies, especially when used in combination.
“ICI myocarditis emerges as an infrequent but potentially fatal condition associated with ICI therapies, especially when used in combination”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [44]
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- Authors
- Moslehi, J., Lichtman, A. H., Sharpe, A. H., Galluzzi, L., & Kitsis, R. N.
- Affiliations
- Vanderbilt University Medical Center (US)
- Brigham and Women's Hospital (US)
- Université Paris Cité (FR)
- Albert Einstein College of Medicine (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2021-03-01
- Volume
- 131
- Issue
- 5
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC7919710
- OpenAlex
- W3134997217
- Cited by
- 237
- References
- 181
- Citations by year
- 2026: 60 · 2025: 46 · 2024: 46 · 2023: 32 · 2022: 40 · 2021: 13
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Defense (PR191593)
- American Heart Association (18SRG34280018)
- Vanderbilt University
- Vanderbilt University Medical Center
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL131862, R01HL130861, R01HL141466, R01HL138475)
- National Institute of Allergy and Infectious Diseases (P01AI056299, P01AI039671)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Keywords
- immune checkpoint inhibitors, immune-related adverse events, T cell-mediated inflammation, predictive biomarkers, diagnostic approach, cancer immunotherapy toxicity
- MeSH terms
- Immune Checkpoint Inhibitors, Humans, Myocarditis, Biomarkers
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