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

• Published in: Cellular physiology and biochemistry Vol. 38; no. 1; pp. 306 - 318
• Main Authors: Wang, Yi, Liu, Taotao, Tang, Wenqing, Deng, Bin, Chen, Yanjie, Zhu, Jimin, Shen, Xizhong
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01-01-2016
• Subjects: Animals; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; CD4 Antigens - metabolism; Cell Line, Tumor; Culture Media, Conditioned - pharmacology; Disease Models, Animal; Female; Forkhead Transcription Factors - metabolism; Foxp3; Hepatocellular carcinoma; Humans; Kaplan-Meier Estimate; Liver Neoplasms - diagnosis; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Mice; Mice, Inbred C57BL; Original Paper; Prognosis; Regulatory T cell; RNA Interference; RNA, Small Interfering - metabolism; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - metabolism; Transforming Growth Factor beta1 - antagonists & inhibitors; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-β1; Transplantation, Homologous; Hepatocellular carcinoma; Prognosis; Transforming growth factor-β1; Foxp3; Regulatory T cell
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000438631

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.