Format

Send to

Choose Destination
  • Unknown field was ignored: [J].
Science. 2018 May 25;360(6391). pii: eaan5931. doi: 10.1126/science.aan5931.

Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells.

Author information

1
Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
3
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
4
Institute of Pathology, University Hospital RWTH Aachen, Aachen 52074, Germany.
5
Institute of Pathology, University Hospital Heidelberg, Heidelberg 69120, Germany.
6
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA.
7
Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
8
Leidos Biomedical Research, Inc, Microbiome Sequencing Core, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
9
Chulabhorn Research Institute, Bangkok, Thailand.
10
NCI CCR Liver Cancer Program, Bethesda, MD, USA.
11
Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. tim.greten@nih.gov.

Abstract

Primary liver tumors and liver metastasis currently represent the leading cause of cancer-related death. Commensal bacteria are important regulators of antitumor immunity, and although the liver is exposed to gut bacteria, their role in antitumor surveillance of liver tumors is poorly understood. We found that altering commensal gut bacteria in mice induced a liver-selective antitumor effect, with an increase of hepatic CXCR6+ natural killer T (NKT) cells and heightened interferon-γ production upon antigen stimulation. In vivo functional studies showed that NKT cells mediated liver-selective tumor inhibition. NKT cell accumulation was regulated by CXCL16 expression of liver sinusoidal endothelial cells, which was controlled by gut microbiome-mediated primary-to-secondary bile acid conversion. Our study suggests a link between gut bacteria-controlled bile acid metabolism and liver antitumor immunosurveillance.

PMID:
29798856
PMCID:
PMC6407885
DOI:
10.1126/science.aan5931
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center