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

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.