Galectin-9缺失对小鼠肿瘤免疫应答的影响  

Tumor immune response in Galectin-9 deficient mice

作　　者：苟娟[1] 黄家君[1] 赵婷婷[2] 高小燕[2] 邢艳[2] 

机构地区：[1]重庆医科大学药学院药理学教研室重庆市生物化学与分子药理学重点实验室,400016 [2]第三军医大学全军免疫学研究所,重庆400038

出　　处：《免疫学杂志》2014年第5期424-427,431,共5页Immunological Journal

基　　金：重庆市科委自然科学基金(CSTC2010BB5111);重庆市教委自然科学基金(KJ100308)

摘　　要：目的在小鼠肿瘤模型中探讨半乳糖凝集素-9(Galectin-9,G9)缺失对肿瘤生长和肿瘤转移的影响,并初步探讨其免疫学机制。方法分别建立B16F10黑色素瘤G9KO-/-C57BL/6小鼠模型和EG7-OVA淋巴瘤G9KO-/-C57BL/6小鼠模型,监测肿瘤体积,绘制肿瘤生长曲线;观察B16F10黑色素瘤G9KO-/-C57BL/6小鼠肺部肿瘤模型转移情况,统计黑色素瘤结节数量;取肿瘤浸润的引流淋巴结(draining lymph node,DLN)流式检测CD8+T淋巴细胞频率及表型。结果 G9KO小鼠相对于WT小鼠能明显抵制B16F10(P<0.05)和EG7(P<0.05)肿瘤的生长,G9KO小鼠能显著抑制黑色素瘤肺部转移(P<0.001);流式检测显示G9KO小鼠能明显下调功能耗竭CD8+T淋巴细胞(Tim-3+,PD-1+Tim-3+)频率(P<0.05,P<0.001)。结论 Galectin-9的缺失能延缓肿瘤的生长,抑制肿瘤的转移,减轻CD8+T细胞耗竭,增强抗肿瘤免疫。In this study, we employed Galectin-9 knockout mice to investigate the role and mechanism of galeetin-9 deficiency on primary tumor growth and tumor metastasis. The implanted tumor models were established by injecting B16F10 melanoma cells or EG7 lymphoma cells in C57BL/6 background G9 knockout mice （G9KO） and wild type mice （WT） subcutaneously. Tumor size was monitored and tumor growth curve was drawn. B16FIO tumor lung metastasis model was established and lung nodules were counted. CD8＋ T-lymphocytes were isolated from tumor-draining lymph node, and their frequency as well as phenotype were analyzed by flow cytometry. In comparison with WT mice, G9KO mice were greatly resistant to B16F10 （P〈 0.05） and EG7 （P〈 0.05） tumor growth and G9KO mice also significantly inhibited B16F10 melanoma lung metastasis （P〈0.001）; G9KO obviously reduced the absolute frequency of functional exhausted CD8＋T lymphoeytes （PD-1＋,Tim-3＋,PD-1＋Tim-3＋） （P〈 0.001）. In conclusion, the lack of galectin-9 could delay tumor growth, inhibit tumor metastasis, and reduce the exhaustion of CD8＋T cell and enhance the anti-tumor immunity.

关 键 词：半乳糖凝集素-9 TIM-3 PD-1 CD8+T细胞 

分 类 号：R392.12[医药卫生—免疫学]