title: Hepatocellular Carcinoma Cells Induce Regulatory T Cells and Lead to Poor Prognosis via Production of Transforming Growth Factor-β1.
abstract: OBJECTIVE
  Regulatory T cells (Tregs) are associated with a poor prognosis in hepatocellular carcinoma (HCC). The purpose of the study was to explore the mechanisms of Tregs accumulation in HCC.
  
  
  METHODS
  We analyzed the frequency of Tregs in HCC by flow cytometry and immunohistochemistry. We also established a transforming growth factor (TGF)-β1-knockdown cell line by lentivirus-mediated RNA interference. Mouse CD4+CD25- T cells were cultured in supernatants from various cell lines.
  
  
  RESULTS
  HCC patients had a high frequency of Tregs, and high numbers of Tregs correlated with a poor prognosis. Liver cancer cells induced Treg production by secreting TGF-β1. In vivo experiments indicated that knockdown of TGF-β1 reduced the numbers of Tregs and metastatic nodules in mice.
  
  
  CONCLUSIONS
  These results indicate that cancer-secreted TGF-β1 may increase Tregs, and TGF-β1 knockdown might impair immunosuppression in the tumor microenvironment by decrease Tregs.
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Taotao
authors.initials: T
authors.lastname: Liu
authors.forename: Wenqing
authors.initials: W
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Chen
authors.forename: Jimin
authors.initials: J
authors.lastname: Zhu
authors.forename: Xizhong
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D015704:CD4 Antigens; D017077:Culture Media, Conditioned; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1