Peer-reviewedCC BY-NC-ND 4.0JACC: CardioOncology
Immune Responses in Checkpoint Inhibitor–Associated Cardiovascular Immune–Related Adverse Events
16 affiliations
- 1Mass General Brigham Cancer Institute, Boston, Massachusetts, USA
- 2Harvard Medical School, Boston, Massachusetts, USA
- 3Broad Institute of MIT and Harvard, Charlestown, Massachusetts, USA
- 4Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, Massachusetts, USA
- 5Heart and Vascular Center, Semmelweis University, Budapest, Hungary
- 6Cardio-Oncology Program, Heart and Vascular Institute, Mass General Brigham, Boston, Massachusetts, USA
- 7Stanford Cardiovascular Institute, Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
- 8Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- 9Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- 10Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- 11Medical Scientist Training Program, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- 12Section of Cardio-Oncology and Immunology, Cardiovascular Research Institute, School of Medicine, University of California-San Francisco, San Francisco, California, USA
- 13Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- 14Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- 15Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- 16Krantz Family Center for Cancer Research, Mass General Brigham Cancer Institute, Boston, Massachusetts, USA
Abstract
Although immune checkpoint inhibitors have improved cancer outcomes, their use can trigger autoimmune toxicities affecting essentially any organ system. In the cardiovascular system, these immune-related adverse events can manifest as myocarditis, pericarditis, accelerated atherosclerosis, vasculitis, arrhythmias, and other conditions. These cardiovascular toxicities are driven by the loss of peripheral tolerance, but the underlying mechanisms remain incompletely understood. Recent murine and human studies, particularly in immune checkpoint inhibitor–associated atherosclerosis and myocarditis, have begun to reveal the cellular and molecular mediators. Disinhibited T cell function is a central driver, but other immune and nonimmune cell types have also been implicated. Multiple inflammatory and chemokine receptor signaling pathways are activated, offering potential targets for intervention. The growing mechanistic understanding of these cardiovascular toxicities has begun to inform new diagnostic and therapeutic strategies, though additional prospective trials are needed.
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BibTeX
@article{reynolds2026immune,
title = {{Immune Responses in Checkpoint Inhibitor–Associated Cardiovascular Immune–Related Adverse Events}},
author = {Kerry L. Reynolds and Alexandra-Chloé Villani and Zsófia Dora Drobni and Tomas G. Neilan and Han Zhu and Noah S. Wagner and Justin M. Balko and Reilly Fankhauser and Javid J. Moslehi and Nicolas L. Palaskas and Kristen E. Pauken and Bilal A. Siddiqui and Steven M. Blum and Daniel A. Zlotoff},
journal = {JACC: CardioOncology},
year = {2026},
month = oct,
doi = {10.1016/j.jaccao.2026.09.005},
url = {https://doi.org/10.1016/j.jaccao.2026.09.005},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Immune Responses in Checkpoint Inhibitor–Associated Cardiovascular Immune–Related Adverse Events
AU - Kerry L. Reynolds
AU - Alexandra-Chloé Villani
AU - Zsófia Dora Drobni
AU - Tomas G. Neilan
AU - Han Zhu
AU - Noah S. Wagner
AU - Justin M. Balko
AU - Reilly Fankhauser
AU - Javid J. Moslehi
AU - Nicolas L. Palaskas
AU - Kristen E. Pauken
AU - Bilal A. Siddiqui
AU - Steven M. Blum
AU - Daniel A. Zlotoff
PY - 2026
DA - 2026/10/01
JO - JACC: CardioOncology
DO - 10.1016/j.jaccao.2026.09.005
UR - https://doi.org/10.1016/j.jaccao.2026.09.005
AB - Although immune checkpoint inhibitors have improved cancer outcomes, their use can trigger autoimmune toxicities affecting essentially any organ system. In the cardiovascular system, these immune-related adverse events can manifest as myocarditis, pericarditis, accelerated atherosclerosis, vasculitis, arrhythmias, and other conditions. These cardiovascular toxicities are driven by the loss of peripheral tolerance, but the underlying mechanisms remain incompletely understood. Recent murine and human studies, particularly in immune checkpoint inhibitor–associated atherosclerosis and myocarditis, have begun to reveal the cellular and molecular mediators. Disinhibited T cell function is a central driver, but other immune and nonimmune cell types have also been implicated. Multiple inflammatory and chemokine receptor signaling pathways are activated, offering potential targets for intervention. The growing mechanistic understanding of these cardiovascular toxicities has begun to inform new diagnostic and therapeutic strategies, though additional prospective trials are needed.
SN - 2666-0873
ER -