Bile acid synthesis impedes tumor-specific T cell responses during liver cancer
Salk Institute for Biological Studies · University of California San Diego · +10 more institutions
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…
Citation impact
- FWCI
- 98.61
- Percentile
- 100%
- References
- 66
Authors
33Topics & keywords
- Ursodeoxycholic acid
- Tumor microenvironment
- Cancer research
- Lithocholic acid
- Bile acid
- Endoplasmic reticulum
- Cancer
- Immunotherapy
- Good health and well-being
Funding
- CRCancer Research Institute
- DRDamon Runyon Cancer Research Foundation
- VUVanderbilt University
- LMLeona M. and Harry B. Helmsley Charitable Trust
- WFWaitt Foundation
- DCDartmouth College
- DCDartmouth Cancer Center
- NINational Institutes of HealthAwards: AI106697, S10-OD023689, OD023689, CA014195, CCSG P30 CA014195, P01 AG073084, P30 014195, P30 CA014195, CCSG P30, AI128949, DK120515, P30 AG068635, KL2TR001444, P30CA23100
- SOSchool of Medicine, Vanderbilt University
- UOUniversity of California, San DiegoAward: KL2TR001444
- NCNational Cancer InstituteAwards: CA014195, AI128949, S10-OD023689, AI106697, P30 CA014195, P30 014195, P30CA23100