【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。更多还原

【Abstract】 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 splenocyte cytotoxicity of LLC were detected by flow cytometry. Tumor growth and survival of tumor bearing mice were recorded. Results On day 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 CD8+T cells were significantly higher than control mice(9.464±0.820 vs 4.024±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.更多还原