IP10对机体抗肿瘤免疫应答的增强作用及其机制

IP10 enhances anti-tumor immunity and its mechanisms

目的:研究IP10对机体整体及肿瘤局部细胞免疫应答的影响,从而探讨其抗肿瘤的作用及机制。方法:基因转染的方法建立稳定表达IP10的4T1细胞株(IP10-4T1)。观察IP10-4T1细胞生长情况,观察荷瘤小鼠的生存情况。3H-TdR掺入法检测细胞免疫应答水平。F icoll密度梯度离心法分离肿瘤浸润淋巴细胞,流式细胞技术检测CXCR3的表达。结果:pcDNA3-IP10转染不影响4T1细胞体外生长。IP10-4T1形成的肿瘤生长明显减慢,瘤重显著减轻,该荷瘤小鼠生存率显著增加(P<0.05)。与对照组比较,IP10-4T1细胞免疫的小鼠脾细胞特异性增殖反应明显(P<0.05)。IP10-4T1细胞形成的肿瘤内CXCR3+细胞浸润增加,肿瘤内分离的淋巴细胞抗原刺激后显著增殖(P<0.05)。结论:IP10可能通过诱导机体细胞免疫应答、促进肿瘤内淋巴细胞浸润并增强肿瘤内淋巴细胞增殖活性介导抗肿瘤作用。

Objective：To investigate the effects of IP10（IFN-γinducible protein 10,CXCL10） on anti-tumor immune response and to explore its mechanisms involved in. Methods：A mammary carcinoma cell line 4T1 was transfected with peDNA3-IP10 （IP10- 4T1 ） by electrophoration and positive clones were screened in the presence of CA18, Growth kinetics of IP10-4T1 ceils was observed in vitro and in vivo. Survival rate among the animals was determined by daily assessment. Proliferation activity of lymphocytes was analyzed with ^3 H-TdR incorporation. The phenotypes of lymphocytes isolated from tumors by ficoll density gradient centrlfugation were assayed by flow cytometry. Results ：The growth rate of IP10-4T1 cells was similar with that of parental 4T1 cells and neo-vector transfected 4T1 cells in vitro. Growth of the tumors formed by IP10-4T1 cells was inhibited in vivo. Compared to those of controls, the size and the weight of the tumors formed by IP10-4T1 cells decreased significantly 35 days post tumor transplantation（ P 〈 0. 05 ）. And the survival rate of IP10-4T1 tumor-bearing mice increased dramatically. In contrast to the controls, the splenocytes from mice inoculated with IP10- 4T1 cells proliferated vigorously after stimulated with specific antigen in vitro（ P 〈 0. 05 ）. Accumulated CXCR3 ^＋T cells were detected in the tumors formed by IP10-4T1 cells. After stimulated with specific antigen, proliferation activity of the infiltrated lymphocytes isolated from IP10-4T1 tumors was much stronger than that of controls（P 〈 0. 05）. Conclusion：IP10 plays a role in anti-tumor immunity by enhancing ceiktlar immune response and promoting infiltration and proliferation of lymphocytes in tumors.