VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8⁺T cells function in the HCC microenvironment.

ABSTRACT: CD8⁺T cells within the tumor microenvironment (TME) are often functionally impaired, which limits their ability to mount effective anti-tumor responses. However, the molecular mechanisms behind this dysfunction remain incompletely understood. Here, we identified valosin-containing protein (VCP) as a key regulator of CD8⁺T cells suppression in hepatocellular carcinoma (HCC). Our findings reveal that VCP suppresses the activation, expansion, and cytotoxic capacity of CD8⁺T cells both in vitro and in vivo, significantly contributing to the immunosuppressive nature of the TME. Mechanistically, VCP stabilizes the expression of glycerol-3-phosphate dehydrogenase 1-like protein (GPD1L), leading to the accumulation of glycerol-3-phosphate (G3P), a downstream metabo

SUBMITTER: Cheng C 

PROVIDER: S-EPMC11758394 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature