Immune-checkpoint inhibitor-mediated myocarditis: CTLA4, PD1 and LAG3 in the heart.

Autor: Munir AZ; Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA., Gutierrez A; Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA.; Yale University School of Medicine, New Haven, CT, USA., Qin J; Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA., Lichtman AH; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Moslehi JJ; Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA. Javid.moslehi@ucsf.edu.
Jazyk: angličtina
Zdroj: Nature reviews. Cancer [Nat Rev Cancer] 2024 Aug; Vol. 24 (8), pp. 540-553. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1038/s41568-024-00715-5
Abstrakt: Immune-checkpoint inhibitors (ICIs) have revolutionized oncology, with nearly 50% of all patients with cancer eligible for treatment with ICIs. However, patients on ICI therapy are at risk for immune-related toxicities that can affect any organ. Inflammation of the heart muscle, known as myocarditis, resulting from ICI targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and PD1 ligand 1 (PDL1) is an infrequent but potentially fatal complication. ICI-mediated myocarditis (ICI-myocarditis) is a growing clinical entity given the widespread use of ICIs, its increased clinical recognition and growing use of combination ICI treatment, a well-documented risk factor for ICI-myocarditis. In this Review, we approach ICI-myocarditis from a basic and mechanistic perspective, synthesizing the recent data from both preclinical models and patient samples. We posit that mechanistic understanding of the fundamental biology of immune-checkpoint molecules may yield new insights into disease processes, which will enable improvement in diagnostic and therapeutic approaches. The syndrome of ICI-myocarditis is novel, and our understanding of immune checkpoints in the heart is in its nascency. Yet, investigations into the pathophysiology will inform better patient risk stratification, improved diagnostics and precision-based therapies for patients.
(© 2024. Springer Nature Limited.)
Databáze: MEDLINE
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