抗Gr-1抗体降低肺癌小鼠髓源性抑制细胞对CD8 + T细胞数量和肿瘤生长的影响
Effect of myeloid-derived suppressor cells reduced by anti-Gr-1 antibody on CD8 + T cell number and tumor growth
摘要目的:探讨通过抗Gr-1抗体降低Lewis肺癌小鼠髓源性抑制细胞(MDSC)对肿瘤生长及对外周血、脾脏、肿瘤组织中CD8 + T细胞数量的影响。 方法:构建小鼠肺癌Lewis细胞荷瘤小鼠模型。每48 h腹腔注射抗Gr-1抗体降低MDSC(观察组),以注射等量0.7% NaCl溶液的模型小鼠为对照组,持续3周。接瘤第7、14、21天分别处死3只小鼠,应用流式细胞仪动态监测各时间点小鼠外周血、脾脏、肿瘤组织中MDSC、CD8 + T细胞的比例;接瘤7 d后,定时测量小鼠皮下肿瘤的长径、短径,监测两组肿瘤大小。 结果:两组肿瘤体积均随时间延长而增长,其中观察组上升趋势相对缓慢,第20天观察组肿瘤体积较对照组小[(1 978±315)mm 3比(1 356±432)mm 3, P=0.001]。接瘤后第7、14、21天,观察组小鼠外周血、脾脏、肿瘤组织中MDSC和CD8 + T细胞比例均低于对照组。两组小鼠外周血中MDSC比例随时间推移均呈上升趋势,其中观察组小鼠MDSC比例上升趋势较对照组缓慢;两组外周血中CD8 + T细胞比例在第7天至第14天均呈现上升趋势,且观察组上升趋势更明显,第14天至第21天两组CD8 + T细胞比例均呈下降趋势。两组小鼠脾脏中MDSC、CD8 + T细胞比例变化趋势均与外周血相似,但对照组CD8 + T细胞比例在第7天至第14天上升趋势较观察组更明显。对照组瘤组织中MDSC比例在第7天至第14天呈上升趋势,第14天至第21天趋于平稳,观察组MDSC比例在第7天至第14天缓慢上升,第14天至第21天呈现下降趋势,两组CD8 + T细胞比例在第7天至第14天均呈上升趋势,第14天至第21天均呈下降趋势。 结论:抗Gr-1抗体可以有效降低Lewis肺癌荷瘤小鼠外周血、脾脏、肿瘤组织的MDSC,抑制肿瘤生长,但也降低了小鼠外周血、脾脏、肿瘤组织内CD8 + T细胞水平。
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abstractsObjective:To explore the effects of reducing myeloid-derived suppressor cells (MDSC) of Lewis lung cancer mice by anti-Gr-1 antibody on tumor growth and CD8 + T cell number in peripheral blood, spleen and tumor tissues. Methods:A mouse Lewis lung cancer cells tumor-bearing mouse model was constructed. MDSC were reduced by intraperitoneal injection of anti-Gr-1 antibody every 48 h (observation group), and model mice injected with equal amount of 0.7% NaCl solution were used as control group, and the injections lasted for 3 weeks. Three mice were killed on days 7, 14 and 21 after tumor inoculation. Flow cytometry was applied to dynamically monitor the proportions of MDSC and CD8 + T cells in the peripheral blood, spleen and tumor tissues of mice at different time points. Seven days after tumor inoculation, the longest and shortes diameters of subcutaneous tumors in mice were measured at regular intervals to monitor the tumor size of both groups. Results:The tumor volume in both groups increased with the extension of time, and the increase trend in the observation group was relatively slow. On day 20, the tumor volume in the observation group was smaller than that in the model group [(1 978±315) mm 3 vs. (1 356±432) mm 3, P = 0.001]. On days 7, 14 and 21 after tumor inoculation, the proportions of MDSC and CD8 + T cells in the peripheral blood, spleen and tumor tissues of mice of the observation group were lower than those of the control group. The proportion of MDSC in the peripheral blood of mice of both groups showed an upward trend over time, with the observation group showing a slower upward trend than the control group. The proportion of CD8 + T cells in the peripheral blood of both groups showed an upward trend from day 7 to day 14, and the observation group showed a more significant upward trend. The proportion of CD8 + T cells in both groups showed a downward trend from day 14 to day 21. The changes in the proportions of MDSC and CD8 + T cells in the spleen of mice of both groups were similar to those in the peripheral blood, but the proportion of CD8 + T cells in the control group showed a more significant upward trend than the observation group from day 7 to day 14. The proportion of MDSC cells in the tumor tissues of the control group showed a significant upward trend from day 7 to day 14, and stabilized from day 14 to day 21. The proportion of MDSC cells in the observation group slowly increased from day 7 to day 14, and decreased from day 14 to day 21. The proportion of CD8 + T cells in both groups showed an upward trend from day 7 to day 14, and decreased from day 14 to day 21. Conclusions:Anti-Gr-1 antibody can effectively reduce MDSC in the peripheral blood, spleen and tumor tissues of Lewis lung cancer tumor-bearing mice, and inhibit tumor growth, but also reduce the level of CD8 + T cells in the peripheral blood, spleen and tumor tissues.
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