Chiu Ying-Ming, Tsai Chung-Lin, Kao Jung-Ta, Hsieh Chin-Tung, Shieh Dong-Chen, Lee Yi-Ju, Tsay Gregory J, Cheng Ken-Sheng, Wu Yi-Ying
Division of Allergy, Immunology & Rheumatology, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
Department of Nursing, College of Medicine & Nursing, Hungkuang University, Taichung, Taiwan, R.O.C.
Anticancer Res. 2018 Apr;38(4):2069-2078. doi: 10.21873/anticanres.12446.
BACKGROUND/AIM: The programmed death 1 (PD-1) receptor and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of tumor infiltrating T lymphocytes in gastric adenocarcinoma patients are not well-defined.
We characterized the expression of PD-1 and PD-L1 in peripheral blood and tumor infiltrating cells and analyzed the association between PD-1/PD-L1 expression and disease progression in a cohort of 60 patients with Helicobacter pylori infection, including 18 with gastric adenocarcinoma, 23 with gastritis, and 19 asymptomatic controls.
Relative to controls, the expression of PD-1 on peripheral blood and tumor infiltrating T cells increased with disease progression. In vitro, T cells induced PD-L1 expression on primary gastric adenocarcinoma epithelial cells in an IFN-γ-dependent manner, which in turn promoted T cells apoptosis. Blocking of PD-L1 reversed this effect.
This study provides evidence for a new therapeutic target in gastric adenocarcinoma patients.
背景/目的：程序性死亡1（PD-1）受体及其配体（PD-L1）在调节宿主免疫反应中起关键作用。然而，该通路对胃腺癌患者肿瘤浸润性T淋巴细胞功能的抑制作用尚不清楚。
我们对60例幽门螺杆菌感染患者（包括18例胃腺癌患者、23例胃炎患者和19例无症状对照者）外周血和肿瘤浸润细胞中PD-1和PD-L1的表达进行了表征，并分析了PD-1/PD-L1表达与疾病进展之间的关联。
相对于对照，外周血和肿瘤浸润性T细胞上PD-1的表达随疾病进展而增加。在体外，T细胞以IFN-γ依赖的方式诱导原发性胃腺癌上皮细胞上PD-L1的表达，这反过来又促进了T细胞凋亡。阻断PD-L1可逆转这种效应。
本研究为胃腺癌患者提供了一个新的治疗靶点的证据。
