肠道菌群如何促进胆管癌发生 | 热心肠日报
Gut microbiome directs hepatocytes to recruit MDSC and promote cholangiocarcinoma
肠道微生物组引导肝细胞招募MDSC，并促进胆管癌的发生
10.1158/2159-8290.CD-20-0304
12-15, Article
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Gut dysbiosis is commonly observed in patients with cirrhosis and chronic gastrointestinal disorders, however, its effect on anti-tumor immunity in the liver is largely unknown. Here we studied how the gut microbiome affects anti-tumor immunity in cholangiocarcinoma. Primary sclerosing cholangitis (PSC) or colitis, two known risk factors for cholangiocarcinoma, which promote tumor development in mice caused an accumulation of CXCR2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). A decrease in gut barrier function observed in mice with PSC and colitis allowed gut derived bacteria and lipopolysaccharide (LPS) to appear in the liver and induced CXCL1 expression in hepatocytes through a TLR4-dependent mechanism and an accumulation of CXCR2+ PMN-MDSC. On the contrary, neomycin treatment blocked CXCL1 expression, PMN-MDSC accumulation and inhibited tumor growth even in the absence of liver disease or colitis. Our study demonstrates that the gut microbiome controls hepatocytes to form an immunosuppressive environment by increasing PMN-MDSC to promote liver cancer.
First Authors:
Qianfei Zhang
Correspondence Authors:
Tim F Greten
All Authors:
Qianfei Zhang,Chi Ma,Yi Duan,Bernd Heinrich,Umberto Rosato,Laurence P Diggs,Lichun Ma,Soumen Roy,Qiong Fu,Zachary J Brown,Simon Wabitsch,Vishal Thovarai,Jianyang Fu,Dechun Feng,Benjamin Ruf,Linda L Cui,Varun Subramanyam,Karen M Frank,Sophie Wang,David E Kleiner,Thomas Ritz,Christian Rupp,Bin Gao,Thomas Longerich,Alexander Kroemer,Xin Wei Wang,Mathuros Ruchirawat,Firouzeh Korangy,Bernd Schnabl,Giorgio Trinchieri,Tim F Greten