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

  1. Author:
    Ma, Chi
    Han, Miaojun
    Heinrich, Bernd
    Fu, Qiong
    Zhang, Qianfei
    Sandhu, Milan
    Agdashian, David
    Terabe, Masaki
    Berzofsky, Jay A.
    Fako, Valerie
    Ritz, Thomas
    Longerich, Thomas
    Theriot, Casey M.
    McCulloch, John A.
    Roy, Soumen
    Yuan, Wuxing
    Thovarai, Vishal
    Sen, Shurjo
    Ruchirawat, Mathuros
    Korangy, Firouzeh
    Wang, Xin Wei
    Trinchieri, Giorgio
    Greten, Tim F.

  2. Author Address

    NCI, Gastrointestinal Malignancy Sect, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.NCI, Lab Human Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.Univ Hosp RWTH Aachen, Inst Pathol, D-52074 Aachen, Germany.Univ Hosp Heidelberg, Inst Pathol, D-69120 Heidelberg, Germany.North Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC 27607 USA.NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.NCI, Leidos Biomed Res Inc, Microbiome Sequencing Core, NIH, Bethesda, MD 20892 USA.Chulabhorn Res Inst, Bangkok, Thailand.NCI CCR Liver Canc Program, Bethesda, MD 20892 USA.
    1. Year: 2018
    2. Date: MAY 25
  2. Journal: SCIENCE
  3. AMER ASSOC ADVANCEMENT SCIENCE,
    1. 360
    2. 6391
    3. Pages: 876-+
  5. Type of Article: Article
  6. ISSN: 0036-8075
  1. 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-gamma 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.

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External Sources

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  2. DOI: 10.1126/science.aan5931
  3. PMID: 29798856
  4. View record in Web of Science®
  5. WOS: 000433039800040

Library Notes

  1. Fiscal Year: FY2017-2018
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