دورية أكاديمية
Lysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity.
العنوان: | Lysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity. |
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المؤلفون: | Turner JA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA.; Medical Scientist Training Program, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Fredrickson MA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., D'Antonio M; Department of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Katsnelson E; Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., MacBeth M; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Van Gulick R; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Chimed TS; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., McCarter M; Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., D'Alessandro A; Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Robinson WA; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Couts KL; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Pelanda R; Department of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Klarquist J; Department of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Tobin RP; Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA., Torres RM; Department of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA. raul.torres@cuanschutz.edu. |
المصدر: | Nature communications [Nat Commun] 2023 Jun 03; Vol. 14 (1), pp. 3214. Date of Electronic Publication: 2023 Jun 03. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Lysophospholipids*/metabolism , CD8-Positive T-Lymphocytes*, Monitoring, Immunologic ; Signal Transduction ; Receptors, Lysophosphatidic Acid/genetics ; Receptors, Lysophosphatidic Acid/metabolism |
مستخلص: | Lysophosphatidic acid (LPA) is a bioactive lipid which increases in concentration locally and systemically across different cancer types. Yet, the exact mechanism(s) of how LPA affects CD8 T cell immunosurveillance during tumor progression remain unknown. We show LPA receptor (LPAR) signaling by CD8 T cells promotes tolerogenic states via metabolic reprogramming and potentiating exhaustive-like differentiation to modulate anti-tumor immunity. We found LPA levels predict response to immunotherapy and Lpar5 signaling promotes cellular states associated with exhausted phenotypes on CD8 T cells. Importantly, we show that Lpar5 regulates CD8 T cell respiration, proton leak, and reactive oxygen species. Together, our findings reveal that LPA serves as a lipid-regulated immune checkpoint by modulating metabolic efficiency through LPAR5 signaling on CD8 T cells. Our study offers key insights into the mechanisms governing adaptive anti-tumor immunity and demonstrates LPA could be exploited as a T cell directed therapy to improve dysfunctional anti-tumor immunity. (© 2023. The Author(s).) |
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معلومات مُعتمدة: | R01 AI143261 United States AI NIAID NIH HHS; T32 AI007405 United States AI NIAID NIH HHS |
المشرفين على المادة: | PG6M3969SG (lysophosphatidic acid) 0 (Lysophospholipids) 0 (Receptors, Lysophosphatidic Acid) |
تواريخ الأحداث: | Date Created: 20230603 Date Completed: 20230605 Latest Revision: 20240326 |
رمز التحديث: | 20240326 |
مُعرف محوري في PubMed: | PMC10239450 |
DOI: | 10.1038/s41467-023-38933-4 |
PMID: | 37270644 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-023-38933-4 |