FOXP3型
车站3
白细胞介素2受体
癌症研究
转化生长因子
PD-L1
免疫系统
细胞毒性T细胞
肿瘤微环境
细胞凋亡
细胞毒性
信号转导
化学
免疫耐受
T细胞
生物
免疫学
细胞生物学
免疫疗法
体外
生物化学
作者
Shasha Song,Pingfan Yuan,Huaxun Wu,Jingyu Chen,Jingjing Fu,Peipei Li,Jing-Tao Lü,Wei Wei
标识
DOI:10.1016/j.intimp.2014.02.027
摘要
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.
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