Hepatocellular Carcinoma Cells Induce Regulatory T Cells and Lead to Poor Prognosis via Production of Transforming Growth Factor-β1.

BACKGROUND/AIMS 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.