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

• DOI: 10.1126/science.aan5931
• Publication Date: 2018-05-24T18:11:24Z
• Authors: Chi Ma; Miaojun Han; Bernd Heinrich; Qiong Fu; Qianfei Zhang; Milan Sandhu; David Agdashian; Masaki Terabe; Jay A. Berzofsky; Valerie Fako; Thomas Ritz; Thomas Longerich; Casey M. Theriot; John A. McCulloch; Soumen Roy; Wuxing Yuan; Vishal Thovarai; Shurjo K. Sen; Mathuros Ruchirawat; Firouzeh Korangy; Xin Wei Wang; Giorgio Trinchieri; Tim F. Greten
• Keywords: Immunosurveillance; Ex vivo

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