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PD-1/PD-L1 Signaling in Non-ICI Myocarditis

Laura I Yousif1, Aukje G Sijtema1, Ymke Appels1

  • 1Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, the Netherlands.

JACC. Basic to Translational Science
|April 19, 2026
PubMed

Insights

Immune checkpoints like PD-1/PD-L1 are crucial in non-ICI myocarditis, not just ICI treatment. Cardiac cells upregulate PD-L1, working with T cells to manage inflammation.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Oncology

Background:

  • Immune checkpoint inhibitors (ICIs) can cause myocarditis, a serious side effect of cancer therapy.
  • The function of immune checkpoints within the heart during inflammatory conditions unrelated to ICIs is not well understood.

Purpose of the Study:

  • To investigate the expression and role of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in the heart during non-ICI-mediated myocarditis.
  • To determine if PD-1/PD-L1 signaling is involved in the cardiac inflammatory response in myocarditis.

Main Methods:

  • Cross-species single-cell/nucleus RNA sequencing analysis comparing murine myocarditis models and human heart samples.
  • In vitro validation using human cell lines.

Main Results:

  • PD-1/PD-L1 signaling is intrinsically part of the myocardial inflammatory response in both murine and human non-ICI myocarditis.
  • Cardiac endothelial cells and fibroblasts showed significant PD-L1 upregulation during myocarditis.
  • This upregulation coincided with peak PD-1 expression on T cells, suggesting a protective mechanism.

Conclusions:

  • Immune checkpoints play a significant role in the pathogenesis of myocarditis, independent of ICI treatment.
  • The PD-1/PD-L1 pathway in cardiac cells represents a potential therapeutic target for managing myocarditis.
Keywords:
PD-1PD-L1cardio-immunologyimmune checkpointmyocarditis

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