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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.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Song S,Yuan P,Wu H,Chen J,Fu J,Li P,Lu J,Wei W

doi

10.1016/j.intimp.2014.02.027

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

117-23

issue

1

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(14)00081-2

journal_volume

20

pub_type

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