title: Tumour-activated liver stromal cells regulate myeloid-derived suppressor cells accumulation in the liver.
abstract: Regulating mechanisms underlying hepatic myeloid-derived suppressor cell (MDSC) accumulation remain to be described. Here, we provide evidence for the involvement of tumour-activated liver stromal cells in the process of hepatic MDSCs migration and accumulation. Our data showed an elevated frequency of MDSCs in the liver of tumour-bearing mice. Moreover, tumour-activated liver stromal cells promote MDSC migration into the liver site. Further investigation indicated higher levels of cytokine and chemokine expression in liver stromal cells after exposure to the tumour-conditioned supernatant. Notably, the expression levels of proinflammatory factors, mainly including macrophage colony stimulating factor (M-CSF), transforming growth factor-β (TGF-β), monocyte chemotactic protein-1 (MCP-1) and stromal-derived factor-1 (SDF-1), increased after treatment with tumour-conditioned supernatant, and blockade of MCP-1 or SDF-1 decreased the proportion of tumour infiltrated MDSCs in mice co-transplanted with liver stromal cells and tumour cells, but not in mice with only tumour cells injection. These findings demonstrate that tumour-activated liver stromal cells produce higher levels of chemokines and cytokines, which may contribute to MDSC accumulation into the liver site in patients with liver cancer.
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.|Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.
authors.forename: G
authors.initials: G
authors.lastname: He
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Jia
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Xie
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing, China.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Wei
authors.affiliation: Institute of Immunology, Tsinghua University School of Medicine, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers; D002450:Cell Communication; D002452:Cell Count; D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000378:metabolism*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D016130:Immunophenotyping; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
chemical_list: D015415:Biomarkers; D018925:Chemokines
keywords: hepatic microenvironment; hepatocellular carcinoma; liver stroma; myeloid-derived suppressor cells