Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.

ABSTRACT: The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. Furthermore, different BAs regulated CD8⁺ T cells differently; primary BAs induced oxidative stress, whereas the secondar

SUBMITTER: Varanasi SK 

PROVIDER: S-EPMC12166762 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature