关键词: 肺癌, 骨髓来源的抑制细胞, CD8+T细胞, 免疫抑制

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.

Key words: Lung carcinoma, Myeloid-derived suppressor cells, CD8+Tcells, Immunosuppression