肺癌小鼠模型中删除MDSCs对CD8+T细胞的影响  

The Influence of MDSC Depletion on CD8+ T Cells in Lung Carcinoma of Mouse Model

作　　者：王慧茹 潘健[1] 

机构地区：[1]安徽省立医院输血科,合肥230001

出　　处：《临床输血与检验》2017年第6期543-546,共4页Journal of Clinical Transfusion and Laboratory Medicine

摘　　要：目的在路易斯肺癌LLC荷瘤小鼠模型中通过删除外周血中骨髓来源的抑制细胞(MDSCs),探讨MDSCs对CD8+T细胞数量和功能、体内肿瘤生长及小鼠生存期的影响。方法将C57小鼠皮下接种LLC,尾静脉注射Gr-1抗体删除荷瘤小鼠血液中的MDSC或注射对照抗体,于不同时间点采尾血,应用流式细胞术检测外周血中MDSC和CD8+T细胞的变化,记录肿瘤生长情况和小鼠生存期,比较两组荷瘤小鼠的脾细胞对LLC细胞的杀伤作用。结果 LLC荷瘤7 d后小鼠中MDSCs比例(%)(23.870±1.350)显著高于正常小鼠(7.600±0.677)(P<0.001),CD8+T细胞比例(%)(7.906±0.428)显著低于正常小鼠(11.220±0.606)(P<0.001);荷瘤7 d注射Gr-1删除抗体或对照抗体,3 d后删除组外周血MDSCs比例(%)较未删除组显著降低(分别为1.578±0.299 vs 38.340±3.214,P<0.001),CD8+T细胞比例(%)显著高于未删除组(分别为9.464±0.820 vs 4.024±0.488,P<0.001);抗体注射10 d后删除组MDSCs比例(%)较之前显著增加(31.980±3.595),但仍然低于普通荷瘤组(63.660±5.763)(P=0.001 6),CD8+T细胞比例(%)较之前降低(5.806±0.554),仍高于普通荷瘤组(2.894±0.330)(P=0.001 9);MDSCs删除组小鼠肿瘤生长减缓(P<0.05)、生存期延长(P=0.036,中位生存期46 d vs 53 d)。结论在LLC荷瘤小鼠中删除MDSC能解除其对CD8+T细胞的抑制,减缓肿瘤生长,延长小鼠生存期。Objective To explore the effect of MDSCs on the number and function of CD8＋T cells, tumor growth in vivo and survival in Lewis lung cancer mice. Methods LLC tumor cells were inoculated into the flank of C57 LB/6 mice. MDSC were depleted by intravenous administration of Gr-1 blocking antibody. Tail blood was collected and CD8＋T cells, MDSCs and splenoeyte eytotoxicity of LLC were detected by flow cytometry. Tumor growth and survival of tumor bearing mice were recorded. Results On clay 7 after tumor inoculation, the percentages of MDSCs from tumor bearing mice were significantly higher than the control （23.87±1.35% vs 7.600±0.677%, P〈0.001） and CD8＋T cells were declined compared with the control （7.906±0.428%） vs （11.22±0.606%, P〈0.001） . Gr-1 blocking antibody was administered to deplete MDSCs. On day 3 after administration, the percentages of MDSCs were rapidly decreased （1.578±0.299% vs 38.34±3.214%, P〈0.001） and CDg＋T cells were significantly higher than control mice （9.464±0.820vs4.024±0.488, P〈0.001） . On day 10 after administration, MDSCs percentages were increased, but decreased when compared to control mice （1.578±0,299%） vs （38.34±3.214%, P=0.0016） and CD8＋T cells were deceased but elevated compared with control mice （9.464±0.820%） vs （ 4.024±0.488%, P=0.0019） . Tumor growth in mice with MDSCs depletion was markedly inhibited compared with control group （P〈0.05） . The survival of mice with MDSCs depletion was notably longer than control mice （P=0.036, median survival 46 vs 53） . Conclusion MDSCs depletion in LLC tumor bearing mice eliminated the inhibition of CD8＋T cells by MDSCs Leading to a restriction of tumor growth and prolonged survival.

关 键 词：肺癌 骨髓来源的抑制细胞 CD8+T细胞 免疫抑制 

分 类 号：R734.2[医药卫生—肿瘤] R392.11[医药卫生—临床医学]