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Lysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity.

التفاصيل البيبلوغرافية
العنوان: Lysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity.
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
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-38933-4