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Int Immunopharmacol. 2014 May;20(1):117-23. doi: 10.1016/j.intimp.2014.02.027. Epub 2014 Mar 4.

Dendritic cells with an increased PD-L1 by TGF-β induce T cell anergy for the cytotoxicity of hepatocellular carcinoma cells.

Author information

1
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Hefei 230032, PR China.
2
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.
3
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.

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.

KEYWORDS:

Cytotoxicity; Dendritic cells; Programmed death ligand-1; Signal transducers and activators of transcription 3; T cell anergy; Transforming growth factor β

PMID:
24606770
DOI:
10.1016/j.intimp.2014.02.027
[Indexed for MEDLINE]

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