Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Science (American Association for the Advancement of Science), 2018-05, Vol.360 (6391)

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2018

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.