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Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells.
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 K; Ruchirawat, Mathuros; Korangy, Firouzeh; Wang, Xin Wei; Trinchieri, Giorgio; Greten, Tim F.
Affiliation
  • Ma C; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Han M; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Heinrich B; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Fu Q; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhang Q; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sandhu M; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Agdashian D; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Terabe M; Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Berzofsky JA; Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Fako V; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Ritz T; Institute of Pathology, University Hospital RWTH Aachen, Aachen 52074, Germany.
  • Longerich T; Institute of Pathology, University Hospital RWTH Aachen, Aachen 52074, Germany.
  • Theriot CM; Institute of Pathology, University Hospital Heidelberg, Heidelberg 69120, Germany.
  • McCulloch JA; Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA.
  • Roy S; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yuan W; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Thovarai V; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sen SK; Leidos Biomedical Research, Inc, Microbiome Sequencing Core, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ruchirawat M; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Korangy F; Leidos Biomedical Research, Inc, Microbiome Sequencing Core, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wang XW; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Trinchieri G; Leidos Biomedical Research, Inc, Microbiome Sequencing Core, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Greten TF; Chulabhorn Research Institute, Bangkok, Thailand.
Science ; 360(6391)2018 05 25.
Article in En | MEDLINE | ID: mdl-29798856
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bile Acids and Salts / Natural Killer T-Cells / Gastrointestinal Microbiome / Immunologic Surveillance / Liver / Liver Neoplasms Limits: Animals / Humans Language: En Journal: Science Year: 2018 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bile Acids and Salts / Natural Killer T-Cells / Gastrointestinal Microbiome / Immunologic Surveillance / Liver / Liver Neoplasms Limits: Animals / Humans Language: En Journal: Science Year: 2018 Document type: Article Affiliation country: