Immune checkpoint inhibitor–associated myocarditis: manifestations and mechanisms
Javid Moslehi,1 Andrew H. Lichtman,2 Arlene H. Sharpe,3,4 Lorenzo Galluzzi,5,6,7 and Richard N. Kitsis8
1Division of Cardiovascular Medicine and Division of Oncology, Cardio-Oncology Program, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
2Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
3Department of Immunology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
4Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, USA.
5Department of Radiation Oncology, Sandra and Edward Meyer Cancer Center, Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, New York, USA.
6Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA.
7Université de Paris, Paris, France.
8Departments of Medicine and Cell Biology, Wilf Family Cardiovascular Research Institute, and Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Address correspondence to: Javid Moslehi, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, Tennessee 37232, USA. Phone: 615.343.9436; Email: javid.moslehi@vumc.org. Or to: Richard N. Kitsis, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. Phone: 718.430.2609; Email: richard.kitsis@einsteinmed.org.
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1Division of Cardiovascular Medicine and Division of Oncology, Cardio-Oncology Program, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
2Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
3Department of Immunology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
4Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, USA.
5Department of Radiation Oncology, Sandra and Edward Meyer Cancer Center, Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, New York, USA.
6Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA.
7Université de Paris, Paris, France.
8Departments of Medicine and Cell Biology, Wilf Family Cardiovascular Research Institute, and Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Address correspondence to: Javid Moslehi, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, Tennessee 37232, USA. Phone: 615.343.9436; Email: javid.moslehi@vumc.org. Or to: Richard N. Kitsis, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. Phone: 718.430.2609; Email: richard.kitsis@einsteinmed.org.
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1Division of Cardiovascular Medicine and Division of Oncology, Cardio-Oncology Program, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
2Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
3Department of Immunology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
4Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, USA.
5Department of Radiation Oncology, Sandra and Edward Meyer Cancer Center, Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, New York, USA.
6Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA.
7Université de Paris, Paris, France.
8Departments of Medicine and Cell Biology, Wilf Family Cardiovascular Research Institute, and Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Address correspondence to: Javid Moslehi, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, Tennessee 37232, USA. Phone: 615.343.9436; Email: javid.moslehi@vumc.org. Or to: Richard N. Kitsis, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. Phone: 718.430.2609; Email: richard.kitsis@einsteinmed.org.
Find articles by Sharpe, A. in: JCI | PubMed | Google Scholar
1Division of Cardiovascular Medicine and Division of Oncology, Cardio-Oncology Program, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
2Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
3Department of Immunology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
4Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, USA.
5Department of Radiation Oncology, Sandra and Edward Meyer Cancer Center, Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, New York, USA.
6Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA.
7Université de Paris, Paris, France.
8Departments of Medicine and Cell Biology, Wilf Family Cardiovascular Research Institute, and Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Address correspondence to: Javid Moslehi, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, Tennessee 37232, USA. Phone: 615.343.9436; Email: javid.moslehi@vumc.org. Or to: Richard N. Kitsis, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. Phone: 718.430.2609; Email: richard.kitsis@einsteinmed.org.
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1Division of Cardiovascular Medicine and Division of Oncology, Cardio-Oncology Program, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
2Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
3Department of Immunology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
4Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, USA.
5Department of Radiation Oncology, Sandra and Edward Meyer Cancer Center, Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, New York, USA.
6Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA.
7Université de Paris, Paris, France.
8Departments of Medicine and Cell Biology, Wilf Family Cardiovascular Research Institute, and Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Address correspondence to: Javid Moslehi, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, Tennessee 37232, USA. Phone: 615.343.9436; Email: javid.moslehi@vumc.org. Or to: Richard N. Kitsis, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. Phone: 718.430.2609; Email: richard.kitsis@einsteinmed.org.
Find articles by Kitsis, R. in: JCI | PubMed | Google Scholar
Published March 1, 2021 - More info
J Clin Invest. 2021;131(5):e145186. https://doi.org/10.1172/JCI145186.
© 2021 American Society for Clinical Investigation
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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