TY - JOUR
T1 - Immune checkpoint inhibitor-associated myocarditis
T2 - Manifestations and mechanisms
AU - Moslehi, Javid
AU - Lichtman, Andrew H.
AU - Sharpe, Arlene H.
AU - Galluzzi, Lorenzo
AU - Kitsis, Richard N.
N1 - Funding Information:
Conflict of interest: JM has served on scientific advisory boards for Bristol Myers Squibb, Takeda, Deciphera, AstraZeneca, Nektar, Audentes Therapeutics, TripleGene, Boston Biomedical, ImmunoCore, Janssen, Myovant, Cytokinetics, and Amgen. AHS is on the scientific advisory boards for Surface Oncology, SQZ Biotech, Elstar Therapeutics, Elpiscience, Selecta, and Monopteros, consults for Novartis, and has research funding from Merck, Novartis, Roche, Ipsen, and Quark Ventures. AHS has patents/ pending royalties from Roche and Novartis on intellectual property on the PD-1 pathway (patent 7,432,059 with royalties paid from Roche, Merck, Bristol-Myers-Squibb, EMD-Serono, Boehringer-Ingelheim, AstraZeneca, Leica, Mayo Clinic, Dako, and No-vartis; patent 7,722,868 with royalties paid from Roche, Merck, Bristol-Myers-Squibb, EMD-Serono, Boehringer-Ingelheim, AstraZeneca, Leica, Mayo Clinic, Dako, and Novartis; patents 8,652,465 and 9,457,080 licensed to Roche; patents 9,683,048, 9,815,898, 9,845,356, 10,202,454. and 10,457,733 licensed to Novartis; and patents 9,580,684, 9,988,452, and 10,370,446 issued to none). LG has received research funding from Lytix and Phosplatin, as well as consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, The Longevity Labs, Inzen, and the Luke Heller TECPR2 Foundation. RNK is cofounder and president of ASPIDA Therapeutics Inc. RNK has a patent (PCT/ US2018/021644) for small-molecule BAX inhibitors. Copyright: © 2021, American Society for Clinical Investigation. Reference information: J Clin Invest. 2021;131(5):e145186. https://doi.org/10.1172/JCI145186.
Funding Information:
This work was supported by the NIH (R01HL141466 to JM, R01HL131862 to AHL, P01AI56299 to AHS, P01AI039671 to AHS, R01H130861 to RNK, and R01HL138475 to RNK); the US Department of Defense (C180476P1 to LG and PR191593 to RNK); the American Heart Association (18SRG34280018 to RNK); and Foundation Leducq (RA15CVD04 to RNK). The authors also acknowledge helpful discussions with Pilar Alcaide, Nikolaos G. Frangogiannis, Sally Huber, Kirk U. Knowlton, Bruce M. McMa-nus, and Sumanth Prabhu.
Publisher Copyright:
© 2021, American Society for Clinical Investigation.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85102141119&partnerID=8YFLogxK
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U2 - 10.1172/JCI145186
DO - 10.1172/JCI145186
M3 - Review article
C2 - 33645548
AN - SCOPUS:85102141119
SN - 0021-9738
VL - 131
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 5
M1 - e145186
ER -
