title: Hepatic stellate cells promote tumor progression by enhancement of immunosuppressive cells in an orthotopic liver tumor mouse model.
abstract: The immunosuppressive properties of hepatic stellate cells (HSCs) contribute to the occurrence and development of hepatocellular carcinoma (HCC). The accumulation of cells with immune suppressive activities, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) is a key mechanism for tumor immune evasion. However, the impact of HSCs on immune cell populations in tumor-bearing hosts is unclear. In this study, we established an orthotopic liver tumor mouse model for studying the complex tumor-host interactions in HCC. The activated HSCs promoted HCC growth not only induced tumor angiogenesis and lymphangiogenesis, but also significantly increased the suppressive immune cell population of Tregs and MDSCs in the spleen, bone marrow, and tumor tissues of the tumor-bearing mice. Murine HCC cell line H22-activated HSCs also expanded the expression of Tregs and MDSCs in vitro. In conclusion, our study suggests a novel role for HSCs in the HCC microenvironment. HSCs can promote HCC progression by enhancement of the immunosuppressive cell population. Targeting HSCs, which is a new concept in adjuvant immunotherapy, may be introduced in the near future to improve the outcome of patients with HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Zhengqi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Guangli
authors.initials: G
authors.lastname: Ren
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Tang
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Penghao
authors.initials: P
authors.lastname: Kuang
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Bixing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma (Xiamen University Affiliated Zhongshan Hospital), Xiamen, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000628:therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D055166:Hepatic Stellate Cells / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019139:Tumor Escape / Q000235:genetics / Q000502:physiology*; D048069:Tumor Necrosis Factors / Q000235:genetics*
chemical_list: D048069:Tumor Necrosis Factors