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- W4297020009 abstract "Abstract 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 differentiation to modulate anti-tumor immunity. We found LPA levels predict response to immunotherapy and Lpar5 signaling drives exhausted phenotypes on CD8 T cells. Importantly, we identify a novel function of Lpar5 to regulate 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 novel T cell directed therapy to improve dysfunctional anti-tumor immunity." @default.
- W4297020009 created "2022-09-25" @default.
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- W4297020009 date "2022-09-23" @default.
- W4297020009 modified "2023-10-12" @default.
- W4297020009 title "Lysophosphatidic acid modulates CD8 T cell immunosurveillance, metabolism, and anti-tumor immunity" @default.
- W4297020009 doi "https://doi.org/10.21203/rs.3.rs-2058360/v1" @default.
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