VEGF诱导致耐受性树突状细胞对口腔鳞状细胞癌患者T细胞免疫功能的影响  

The impact of tolerogenic dendritic cell induced by VEGF on T lymphocyte immune function in patients with oral squamous cell carcinoma

作　　者：董斌 张兵 封亚萍 韩彦博 杨新华 于兵兵 DONG Bin;ZHANG Bing;FENG Yaping;HAN Yanbo;YANG Xinhua;YU Bingbing(Department of Maxillofacial Surgery,Pingdingshan Stomatological Hospital,Pingdingshan 467000,He＇nan,China;Department of Ontology;Department of Pathology,the PLA No.152 Central Hospital,Pingdingshan 467000,He＇nan,China)

机构地区：[1]平顶山市口腔医院颌面外科,河南平顶山467000 [2]解放军第一五二中心医院肿瘤科,河南平顶山4670000 [3]解放军第一五二中心医院病理科,河南平顶山4670000

出　　处：《癌症进展》2018年第9期1111-1115,共5页Oncology Progress

摘　　要：目的探讨口腔鳞状细胞癌微环境中的血管内皮细胞生长因子(VEGF)诱导致耐受性树突状细胞(DC)对T细胞增殖活性和免疫功能的影响。方法体外培养SCC-4口腔鳞癌细胞株,采用酶联免疫吸附测定(ELISA)法检测SCC-4细胞培养上清中VEGF的相对表达量;采用流式细胞术(FCM)检测DC表面特异性分子的表达情况;采用混合淋巴细胞反应(MLR)检测各组DC对同种异源T细胞增殖活性的影响;采用FCM检测未成熟DC中总吲哚胺-2,3-双加氧酶(IDO)和程序性死亡受体配体1(PDCD1LG1,也称PD-L1)的表达情况。结果培养72 h后,SCC-4细胞培养上清中VEGF的相对表达量高于24、48 h时SCC-4细胞培养上清中VEGF的相对表达量(P﹤0.05)。与空白对照组比较,VEGF组、共培养组和抗VEGF组DC表面特异性分子CD11c、CD80、CD86、CD40、MHCⅡ的表达水平及细胞培养上清中IL-12的表达水平均有所降低(P﹤0.05);但是,共培养组和抗VEGF组DC表面特异性分子的表达水平却均稍高于VEGF组,差异均有统计学意义(P﹤0.05)。在相同比例下,T细胞对照组和抗VEGF组未成熟DC刺激T细胞的增殖活性均高于VEGF组和共培养组,且T细胞对照组刺激T细胞的增殖能力高于抗VEGF组(P﹤0.05)。与T细胞对照组比较,VEGF组、共培养组和抗VEGF组中未成熟DC表面IDO和PD-L1的表达水平均有所升高(P﹤0.05),而共培养组未成熟DC表面IDO和PD-L1的表达水平最高。抗IDO组、抗PD-L1组和抗IDO+PD-L1组未成熟DC刺激T细胞的增殖活性均高于T细胞对照组(P﹤0.05);其中,抗IDO+PD-L1组未成熟DC刺激T细胞的增殖活性最高。结论肿瘤微环境中的VEGF通过刺激IDO和PDL1的表达,抑制小鼠髓样DC的分化,使其成为致耐受性DC,从而抑制T细胞免疫功能。Objective To investigate the impact of tolerogenic dendritic cell（DC） induced by vascular endothelial growth factor（VEGF） on T lymphocyte immune function in patients with oral squamous cell carcinoma. Method SCC-4 cells were cultured in vitro and the supernatant VEGF level was detected by ELISA. The expressions of specific molecules on surface of DC were analyzed by flow cytometry（FCM）. The effect of DC on proliferation activity of allogenic T lymphocyte in each group was tested by mixed lymphocyte reaction（MLR）. The expression levels of indole-2,3-doxygenase（IDO） and programmed cell death 1 ligand 1（PD-L1） in immature DC were detected by FCM. Result With the extension of culture time, the level of VEGF in cell culture supernatant after culturing for 72 h was significantly higher than VEGF levels after culturing for 24 h or 48 h（P0.05）. In VEGF group, co-cultured group and anti-VEGF group, the expressions of specific molecules on surface of DC, including CD11 c, CD80, CD86, CD40 MHCⅡ, and IL-12 level in cell culture supernatant, were all significantly lower than those in blank control group（P0.05）; but the expressions of these specific molecules on surface of DC and the IL-12 level in cell culture supernatant in co-cultured group and anti-VEGF group were higher than those in VEGF group（P0.05）. Under the same proportion, the stimulatory capacity of immature DC to T cell proliferation in control group and anti-VEGF group was higher than that in VEGF group and co-cultured group, and it was higher in control group than that in anti-VEGF group（P0.05）. The expression levels of IDO and PDL1 in immature DC in VEGF group, co-cultured group and anti-VEGF group were significantly higher than those in control group（P0.05）. The stimulatory capacity of immature DC to T cell proliferation in anti-IDO group, anti-PD-L1 group and anti-IDO＋PD-L1 group was significantly higher than that in control group（P0.05）, and it was the highest in anti-IDO＋PD-L1 group. Conclusion The VEGF

关 键 词：血管内皮细胞生长因子 树突状细胞 T细胞 口腔鳞状细胞癌 肿瘤微环境 

分 类 号：R739.8[医药卫生—肿瘤]