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

Yi Wang; Taotao Liu; Wenqing Tang; Bin Deng; Yanjie Chen; Jimin Zhu; Xizhong Shen

doi:10.1159/000438631

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

Cell Physiol Biochem. 2016;38(1):306-18. doi: 10.1159/000438631. Epub 2016 Jan 25.

Authors

Yi Wang¹, Taotao Liu, Wenqing Tang, Bin Deng, Yanjie Chen, Jimin Zhu, Xizhong Shen

Affiliation

¹ Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

PMID: 26799063
DOI: 10.1159/000438631

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4 Antigens / metabolism
Carcinoma, Hepatocellular / diagnosis
Carcinoma, Hepatocellular / mortality
Carcinoma, Hepatocellular / pathology*
Cell Line, Tumor
Culture Media, Conditioned / pharmacology
Disease Models, Animal
Female
Forkhead Transcription Factors / metabolism
Humans
Kaplan-Meier Estimate
Liver Neoplasms / diagnosis
Liver Neoplasms / mortality
Liver Neoplasms / pathology*
Lung Neoplasms / pathology
Lung Neoplasms / secondary
Mice
Mice, Inbred C57BL
Prognosis
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*
Transplantation, Homologous

Substances

CD4 Antigens
Culture Media, Conditioned
FOXP3 protein, human
Forkhead Transcription Factors
RNA, Small Interfering
Transforming Growth Factor beta1