中文摘要：

目的观察tm TNF-α/TNFR2信号轴对荷瘤鼠肿瘤生长影响及其机制。方法采用Western blot检查H22荷瘤鼠肿瘤微环境中Treg细胞TNFR1及TNFR2的表达。TNFR2敲除BALB/c小鼠和野生型鼠各10只,在TNFR2敲除的BALB/c小鼠皮下接种H22肝癌细胞株,观察肿瘤直径及肿瘤微环境中Treg的募集数量,同时以野生型小鼠做对照。用tm TNF-α刺激Treg细胞,ELISA检测上清IL-10和TGF-β的含量。结果荷瘤鼠微环境中Treg细胞TNFR2表达明显高于野生型小鼠脾脏Treg细胞（P〈0.05）,而TNFR1表达未见明显变化;TNFR2基因敲除鼠肿瘤直径明显低于野生型小鼠（P〈0.05）,且肿瘤微环境中Treg细胞数量也明显少于野生型小鼠（P〈0.05）。在体外tm TNF-α可以促进Treg细胞产生IL-10和TGF-β（P〈0.05）。结论 TNFR2基因敲除小鼠肿瘤生长减缓,肿瘤局部微环境中Treg细胞减少,同时tm TNF-α能够刺激Treg细胞释放抑炎因子IL-10和TGF-β,增强其免疫抑制功能。

英文摘要：

Objective To determine the effect of the transmembrane TNF-α /tumor necrosis factor receptor 2（ tm TNF-α / TNFR2） signaling axis on the growth of transplantation tumor in mouse xenograft model and investigate the underlying mechanism. Methods Western blotting was used to determine the expression of TNFR1 and TNFR2 in the Treg cells from control mice and H22 tumor-bearing mice. TNFR2 knock-out mice and wild-type mice（ 10 animals in each group） were subcutaneously inoculated with H22 hepatocarcinoma cells,then the tumor growth as well as the accumulation of Treg in the suspension of tumor cells were observed. IL-10 and TGF-β production in Treg cells in response to the exogenous tm TNF-α were detected by ELISA. Results The TNFR2 expression was significantly higher in the Treg cells from the tumor microenvironment in the tumor-bearing mice than in the spleen Treg cells from wild-type mice（ P〈0. 05）,but no significant change was seen in the TNFR1 expression. Tumor size was obviously smaller in the TNFR2- /-tumor-bearing mice than the wild-type tumor-bearing mice（ P〈0. 05）,and the percentage of Treg in the tumor microenvironment was remarkably less in the former group of mice than the latter（ P〈0. 05）.Exogenous tm TNF-α promoted the secretion of IL-10 and TGF-β in Treg cells（ P〈0. 05）. Conclusion The transplanted tumor gowns slowly in TNFR2 knockout mice, with reduced Treg cells in the tumor microenvironments. tm TNF-α stimulates the release of anti-inflammatory cytokines IL-10 and TGF-β in the Treg cells to enhance the immune response.