Progenitor exhausted PD-1+ T cells are cellular targets of immune checkpoint inhibition in atherosclerosis
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| Title: | Progenitor exhausted PD-1+ T cells are cellular targets of immune checkpoint inhibition in atherosclerosis |
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| Authors: | Mulholland, Megan, Chalou, Anthi, Andersson, Samuel H A, Depuydt, Marie A C, Yu, Yinda, Lin, Shiying, Tallbäck, Klara, Ericsson, Astrid, Jakobsson, Gabriel, de Mol, Jill, Kryvokhyzha, Dmytro, Lichtman, Andrew H, Foks, Amanda C, Schiopu, Alexandru, Björkbacka, Harry, Slütter, Bram, Gisterå, Anton, Engelbertsen, Daniel |
| Contributors: | Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Cardiovascular research - Immune regulation, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Kardiovaskulär forskning - immunreglering, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EXODIAB: Excellence of Diabetes Research in Sweden, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EXODIAB: Excellence of Diabetes Research in Sweden, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Cardiovascular Research - Immunity and Atherosclerosis, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Kardiovaskulär forskning - immunitet och ateroskleros, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Cardiovascular Research - Cellular Metabolism and Inflammation, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Kardiovaskulär forskning - cellulär metabolism och inflammation, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Clinical Genetics, Synthetic Immunology, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för klinisk genetik, Syntetisk immunologi, Originator, Lund University, Faculty of Medicine, Department of Translational Medicine, Cardiac Inflammation Research Group, Lunds universitet, Medicinska fakulteten, Institutionen för translationell medicin, Hjärtinflammationsforskningsgrupp, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Diabetic Complications, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Diabetiska komplikationer, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EpiHealth: Epidemiology for Health, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EpiHealth: Epidemiology for Health, Originator, Lund University, Faculty of Medicine, Faculty Office - BMC, The Education Office, Division of Course Administration for the Medical Programme, Teachers at the Medical Programme, Lunds universitet, Medicinska fakulteten, Kansli M, Utbildningsenheten, Avdelningen för läkarprogrammets kursadministration, Lärare vid läkarprogrammet, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Cardiovascular Research - Matrix and Inflammation in Atherosclerosis, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Kardiovaskulär forskning - matrix och inflammation i ateroskleros, Originator |
| Source: | Nature Cardiovascular Research. |
| Subject Terms: | Medical and Health Sciences, Clinical Medicine, Cardiology and Cardiovascular Disease, Medicin och hälsovetenskap, Klinisk medicin, Kardiologi och kardiovaskulära sjukdomar |
| Description: | 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-1 intSlamf6 +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-1 high T cell accumulation, IFNγ production, formation of lymphocyte foci and neutrophil recruitment. Depletion of PD-1 high T cells prior to PD-1 blockade did not impede T cell recruitment, suggesting a role for progenitor exhausted PD-1 int 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. |
| Access URL: | https://doi.org/10.1038/s44161-025-00713-2 |
| Database: | SwePub |
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