Scholarlink

<p>Immune checkpoint inhibitors (ICIs), targeting checkpoint receptors such as programmed cell death protein 1 (PD-1), are associated with increased risk of cardiovascular events, but the underlying mechanisms remain poorly understood. Here we show that PD-1<sup>+</sup> T cells from murine atherosclerotic aortas mainly display a progenitor exhausted phenotype (PD-1<sup>int</sup>Slamf6<sup>+</sup>Tim3<sup>−</sup>), produce IFNγ in vivo, exhibit signs of recent proliferation and maintain polyfunctionality. PD-1 blockade induced marked changes in plaque immune phenotype, with increased PD-1<sup>high</sup> T cell accumulation, IFNγ production, formation of lymphocyte foci and neutrophil recruitment. Depletion of PD-1<sup>high</sup> T cells prior to PD-1 blockade did not impede T cell recruitment, suggesting a role for progenitor exhausted PD-1<sup>int</sup> T cells in ICI-driven T cell plaque accumulation. Human circulating PD-1<sup>+</sup> T cells produced IFNγ and were associated with subclinical coronary atherosclerosis. Our studies highlight IFNγ-producing PD-1<sup>+</sup> T cells as a potential key immune cell population mediating increased cardiovascular risk in patients with cancer receiving ICI.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Progenitor exhausted PD-1+ T cells are cellular targets of immune checkpoint inhibition in atherosclerosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月7日

查看全文
  • Megan Mulholland,
  • Anthi Chalou,
  • Samuel H. A. Andersson,
  • Marie A. C. Depuydt,
  • Yinda Yu,
  • Shiying Lin,
  • Klara Tallbäck,
  • Astrid Ericsson,
  • Gabriel Jakobsson,
  • Jill de Mol,
  • Dmytro Kryvokhyzha,
  • Andrew H. Lichtman,
  • Amanda C. Foks,
  • Alexandru Schiopu,
  • Harry Björkbacka,
  • Bram Slütter,
  • Anton Gisterå,
  • Daniel Engelbertsen

摘要

Immune checkpoint inhibitors (ICIs), targeting checkpoint receptors such as programmed cell death protein 1 (PD-1), are associated with increased risk of cardiovascular events, but the underlying mechanisms remain poorly understood. Here we show that PD-1+ T cells from murine atherosclerotic aortas mainly display a progenitor exhausted phenotype (PD-1intSlamf6+Tim3−), produce IFNγ in vivo, exhibit signs of recent proliferation and maintain polyfunctionality. PD-1 blockade induced marked changes in plaque immune phenotype, with increased PD-1high T cell accumulation, IFNγ production, formation of lymphocyte foci and neutrophil recruitment. Depletion of PD-1high T cells prior to PD-1 blockade did not impede T cell recruitment, suggesting a role for progenitor exhausted PD-1int T cells in ICI-driven T cell plaque accumulation. Human circulating PD-1+ T cells produced IFNγ and were associated with subclinical coronary atherosclerosis. Our studies highlight IFNγ-producing PD-1+ T cells as a potential key immune cell population mediating increased cardiovascular risk in patients with cancer receiving ICI.