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Dryad

Metabolomic analysis of cultured TRAMP-C2 cells in the presence or absence of PD-L1 expression

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Jun 11, 2024 version files 214.82 KB

Abstract

The interaction between the immune inhibitory receptor PD-1 and its ligand PD-L1 is a critical mechanism for altering immune responses, especially during chronic antigen exposures such as cancer. While much research has focused on the PD-1 receptor, recent evidence suggests that PD-L1 can have cell-intrinsic effects in cancer and immune cells. These functions are distinct from its ability to bind and trigger PD-1 activity and are notable given that PD-L1 is widely expressed in mammals. One such cell-intrinsic function is the modulation of cellular metabolism, including regulation of mTOR activity and glycolysis. As part of our investigation into PD-L1 function, we analyzed the metabolome of cultured mouse prostate cancer cells (TRAMP-C2) expressing PD-L1 or with PD-L1 deleted via CRISPR/Cas9. We quantified 186 water-soluble metabolites from TRAMP-C2 cells expressing PD-L1 or not to better understand what metabolic pathways and processes are regulated by PD-L1 expression/activity. We found a broad range of differentially abundant metabolites, most notably a decreased abundance of glycolytic metabolites when PD-L1 expression is knocked out. In our manuscript, we show that this has a functional outcome on viral infection and cytokine signaling.