title: Dendritic cells with an increased PD-L1 by TGF-β induce T cell anergy for the cytotoxicity of hepatocellular carcinoma cells.
abstract: The effects of TGF-β on dendritic cells (DCs) in the tumor microenvironment are not well-understood. In this study, we investigated the effect of TGF-β on the induction of programmed death ligand-1 (PD-L1) expression in DCs and the underlying mechanism, and we further investigated the influence of the DCs with PD-L1 expression altered by TGF-β on T-cell immunity. We determined that TGF-β increased the expression of PD-L1 and signal transducers and activators of transcription 3 (STAT3) in DCs in both a time- and dose-dependent manner, and the expression of PD-L1 was decreased significantly after STAT3 blockade. In addition, TGF-β-treated DCs induced the apoptosis of T cells and increased the percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). Furthermore, the cytotoxicity of T cells against mice hepatocellular carcinoma cells (Hepa) was obviously suppressed. These results suggest that PD-L1 may play an important role in TGF-β-induced immune dysfunction, which finally results in a failure in the anti-tumor responses, and the TGF-β-STAT3-PD-L1 signaling pathway may contribute to novel therapeutic targets for the tumor based on DCs.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei 230032, PR China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Song
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei 230032, PR China.
authors.forename: Pingfan
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei 230032, PR China.
authors.forename: Huaxun
authors.initials: H
authors.lastname: Wu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei 230032, PR China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei 230032, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Fu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei 230032, PR China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei 230032, PR China. Electronic address: lujt126@126.com.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei 230032, PR China. Electronic address: wwei@ahmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000276:immunology*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002470:Cell Survival; D017635:Clonal Anergy; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D008113:Liver Neoplasms; D008297:Male; D008807:Mice, Inbred BALB C; D050796:STAT3 Transcription Factor / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016212:Transforming Growth Factor beta
keywords: Cytotoxicity; Dendritic cells; Programmed death ligand-1; Signal transducers and activators of transcription 3; T cell anergy; Transforming growth factor β