1. Immune checkpoint landscape of human atherosclerosis and influence of cardiometabolic factors.
- Author
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Barcia Durán JG, Das D, Gildea M, Amadori L, Gourvest M, Kaur R, Eberhardt N, Smyrnis P, Cilhoroz B, Sajja S, Rahman K, Fernandez DM, Faries P, Narula N, Vanguri R, Goldberg IJ, Fisher EA, Berger JS, Moore KJ, and Giannarelli C
- Subjects
- Humans, Carotid Artery Diseases immunology, Carotid Artery Diseases metabolism, Cardiometabolic Risk Factors, Diabetes Mellitus, Type 2 immunology, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 drug therapy, Programmed Cell Death 1 Receptor metabolism, Signal Transduction, Lymphocyte Activation Gene 3 Protein, Antigens, CD metabolism, Male, Immune Checkpoint Proteins metabolism, Immune Checkpoint Proteins genetics, CTLA-4 Antigen metabolism, Female, Atherosclerosis immunology, Atherosclerosis metabolism, Aged, Immune Checkpoint Inhibitors adverse effects, Immune Checkpoint Inhibitors therapeutic use, Plaque, Atherosclerotic metabolism, Plaque, Atherosclerotic pathology, Plaque, Atherosclerotic immunology, Coronary Artery Disease immunology, Coronary Artery Disease metabolism
- Abstract
Immune checkpoint inhibitor (ICI) therapies can increase the risk of cardiovascular events in survivors of cancer by worsening atherosclerosis. Here we map the expression of immune checkpoints (ICs) within human carotid and coronary atherosclerotic plaques, revealing a network of immune cell interactions that ICI treatments can unintentionally target in arteries. We identify a population of mature, regulatory CCR7
+ FSCN1+ dendritic cells, similar to those described in tumors, as a hub of IC-mediated signaling within plaques. Additionally, we show that type 2 diabetes and lipid-lowering therapies alter immune cell interactions through PD-1, CTLA4, LAG3 and other IC targets in clinical development, impacting plaque inflammation. This comprehensive map of the IC interactome in healthy and cardiometabolic disease states provides a framework for understanding the potential adverse and beneficial impacts of approved and investigational ICIs on atherosclerosis, setting the stage for designing ICI strategies that minimize cardiovascular disease risk in cancer survivors., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)- Published
- 2024
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