Yi Wang1, Bin Deng, Wenqing Tang, Taotao Liu, Xizhong Shen. 1. The Department of Gastroenterology of Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, People's Republic of China.
Abstract
AIM: The purpose of this study was to explore the mechanisms of TGF-β1 mediated immunosuppression in tumor stroma. METHODS: The expression of TGF-β1 was investigated in Huh7, Hep 3B, SGC-7901, Eca-109 and Hepa1-6 cell lines using immunofluorescence. Knocked-down TGF-β1 of the Hepa1-6 cell line was established through lentivirus-based RNA interference. The interference efficiency of the TGF-β1 gene was tested by real-time PCR and ELISA; the expression of Foxp3, IFN-γ and CD83 in CD4(+), CD8(+) or dendritic cells was examined via flow cytometry; and the tumorigenic ability of the cancer cells was investigated in the animal experiments. RESULTS: The diverse digestive cancer cells were found to secrete TGF-β1, mRNA of which was knocked down by 78 % thanks to lentivirus-based interference in Hepa1-6 cells. Flow cytometry showed that CD4(+)CD25(+)Foxp3(+) regulatory T cells significantly increased in hepatocellular carcinoma patients when compared with those in the healthy controls. The supernatant from Hepa1-6 cells and recombinant TGF-β1 significantly induced the expression of Foxp3 gene in vitro, while that from sh TGF-β1 Hepa1-6 cells restored it. Hepa1-6 cells inhibited IFN-γ and CD83 expression in CD8(+) or dendritic cells by secreting TGF-β1. The animal experiments indicated that the knockdown TGF-β1 gene impaired the tumorigenic ability of Hepa1-6 cells. CONCLUSION: TGF-β1, expressed in cancer cells, might be a potential therapeutic target for cancer treatment.
AIM: The purpose of this study was to explore the mechanisms of TGF-β1 mediated immunosuppression in tumor stroma. METHODS: The expression of TGF-β1 was investigated in Huh7, Hep 3B, SGC-7901, Eca-109 and Hepa1-6 cell lines using immunofluorescence. Knocked-down TGF-β1 of the Hepa1-6 cell line was established through lentivirus-based RNA interference. The interference efficiency of the TGF-β1 gene was tested by real-time PCR and ELISA; the expression of Foxp3, IFN-γ and CD83 in CD4(+), CD8(+) or dendritic cells was examined via flow cytometry; and the tumorigenic ability of the cancer cells was investigated in the animal experiments. RESULTS: The diverse digestive cancer cells were found to secrete TGF-β1, mRNA of which was knocked down by 78 % thanks to lentivirus-based interference in Hepa1-6 cells. Flow cytometry showed that CD4(+)CD25(+)Foxp3(+) regulatory T cells significantly increased in hepatocellular carcinomapatients when compared with those in the healthy controls. The supernatant from Hepa1-6 cells and recombinant TGF-β1 significantly induced the expression of Foxp3 gene in vitro, while that from sh TGF-β1 Hepa1-6 cells restored it. Hepa1-6 cells inhibited IFN-γ and CD83 expression in CD8(+) or dendritic cells by secreting TGF-β1. The animal experiments indicated that the knockdown TGF-β1 gene impaired the tumorigenic ability of Hepa1-6 cells. CONCLUSION: TGF-β1, expressed in cancer cells, might be a potential therapeutic target for cancer treatment.
Authors: Ming O Li; Yisong Y Wan; Shomyseh Sanjabi; Anna-Karin L Robertson; Richard A Flavell Journal: Annu Rev Immunol Date: 2006 Impact factor: 28.527
Authors: Joseph P Erinjeri; Gabriel C Fine; Gosse J Adema; Muneeb Ahmed; Julius Chapiro; Martijn den Brok; Rafael Duran; Stephen J Hunt; D Thor Johnson; Jens Ricke; Daniel Y Sze; Beau Bosko Toskich; Bradford J Wood; David Woodrum; S Nahum Goldberg Journal: Radiology Date: 2019-04-23 Impact factor: 11.105