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  • Review Article
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Cardiotoxicity of T cell immunotherapies

Nature Reviews Cardiology (2026)Cite this article

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Abstract

T cell immunotherapies offer a new approach to cancer therapy. Chimeric antigen receptor (CAR) T cell therapy is the most prolific of these treatments, leveraging genetically engineered T cells to augment the antitumour response. Bispecific antibodies, T cell receptor-engineered T cells and tumour-infiltrating lymphocytes have also emerged as novel T cell therapies with therapeutic benefit. As the variety of T cell therapies and indications for their use expand, a nuanced understanding of potential haemodynamic sequelae and cardiovascular toxicities is required. T cell activation can lead to massive cytokine release and excessive inflammation, termed cytokine release syndrome (CRS). Like other inflammatory syndromes, CRS can lead to cardiovascular complications, including arrhythmias, myocardial infarction and heart failure, with an incidence of cardiovascular events as high as 20% among patients who develop high-grade CRS. In this Review, we summarize the mechanisms, epidemiology and management of T cell therapy-associated CRS and subsequent cardiotoxicity. We also explore how an improved understanding of CAR T cell therapy, and other emerging T cell-based treatments, will inform the prevention and management of adverse cardiovascular events.

Key points

  • Chimeric antigen receptor (CAR) T cell therapy is an expanding class of cellular immunotherapy that uses adoptive transfer of genetically engineered T cells to augment efficient antitumour responses.

  • Other T cell therapies — bispecific antibodies, tumour-infiltrating lymphocytes and T cell receptor-engineered T cells — can also cause cardiotoxicity, but the mechanisms and inflammatory pathways are distinct for each therapy.

  • T cell immunotherapies, particularly CAR T cell therapy, carry a risk of cardiovascular toxicity, primarily driven by systemic inflammation and cytokine release syndrome (CRS).

  • T cell therapies have no cardiovascular contraindications, and pretherapy cardiovascular evaluation is highly individualized, including assessment of cardiovascular risk factors, pre-existing cardiovascular disease and previous exposure to cardiotoxic therapies.

  • Data indicate the central role of IL-6 in the pathophysiology of CAR T cell-related adverse events, and IL-6 blockade with tocilizumab has been used to prevent and treat severe CRS.

  • CRS severity seems to be the strongest predictor of cardiotoxicity, and strategies aimed at preventing high-grade CRS could be key to lowering the risk of cardiovascular complications.

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Fig. 1: Timeline of FDA approval for chimeric antigen receptor T cell therapies.
Fig. 2: Mechanism of CAR T cell therapy.
Fig. 3: Mechanisms of other novel T cell therapies.
Fig. 4: Mechanisms of cardiotoxicity in CAR T cell therapy.

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Acknowledgements

D.A. reports research grants from the American Heart Association, the Cancer Prevention and Research Institute of Texas, the National Institutes of Health (K23HL155890, R01CA301579, R01HL168045 and R01HL170038) and the Robert Wood Johnson Foundation.

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Author notes

  1. These authors contributed equally: Michael A. Raddatz, Ashley F. Stein-Merlob.

Authors and Affiliations

  1. UCLA Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California, Los Angeles, CA, USA

    Michael A. Raddatz, Ashley F. Stein-Merlob & Eric H. Yang

  2. Catholic Health Cardio-Oncology Program, Division of Cardiology, Department of Medicine, St. Francis Medical Center, Roslyn, NY, USA

    Syed S. Mahmood

  3. Lahey Health Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Lahey Hospital and Medical Center, Burlington, MA, USA

    Sarju Ganatra

  4. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Daniel Addison

  5. UCLA Jonsson Comprehensive Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of California, Los Angeles, CA, USA

    Tasha L. Lin & Sarah M. Larson

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Contributions

M.A.R., A.F.S.-M. and E.H.Y. researched data for the article. M.A.R., A.F.S.-M., T.L.L. and E.H.Y. discussed the content of the article. All the authors wrote the manuscript and reviewed/edited it before submission.

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Correspondence to Eric H. Yang.

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Competing interests

E.H.Y. reports research grants from Amgen, Bristol Myers Squibb, Janssen Research and Development, and Novo Nordisk; consulting fees from Edwards Lifesciences and Xencor; and honoraria from Zoll Medical. The other authors declare no competing interests.

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Raddatz, M.A., Stein-Merlob, A.F., Mahmood, S.S. et al. Cardiotoxicity of T cell immunotherapies. Nat Rev Cardiol (2026). https://doi.org/10.1038/s41569-026-01265-z

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