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

• DOI: 10.1016/j.intimp.2014.02.027
• Publication Date: 2014-03-04T17:31:06Z
• Authors: Shasha Song; Pingfan Yuan; Huaxun Wu; Jingyu Chen; Jingjing Fu; Peipei Li; Jingtao Lu; Wei Wei
• Keywords: Clonal Anergy; Male; STAT3 Transcription Factor; 0301 basic medicine; Mice, Inbred BALB C; Carcinoma, Hepatocellular; Cell Survival; T-Lymphocytes; Liver Neoplasms; Dendritic Cells; B7-H1 Antigen; Coculture Techniques; 3. Good health; 03 medical and health sciences; Transforming Growth Factor beta; Cell Line, Tumor; Animals

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.