miR-150对T细胞PD-1表达及肺肿瘤生长的影响  

Effects of miR-150 on expression of PD-1 in T cells and growth of lung tumor

作　　者：张婷 郭晗 郑爱华[3] 张爱红[3] 郑全辉 ZHANG Ting;GUO Han;ZHENG Aihua;ZHANG Aihong;ZHENG Quanhui(Hebei Key Laboratory for Chronic Diseases,School of Basic Medical Sciences,North China University of Science and Technology,Tangshan 063210,China;School of Basic Medical Sciences,North China University of Science and Technology,Tangshan 063210,China;Tangshan Workers'Hospital,Tangshan 063000,China)

机构地区：[1]华北理工大学基础医学院,河北省慢性疾病基础医学重点实验室,唐山063210 [2]华北理工大学基础医学院,唐山063210 [3]唐山市工人医院,唐山063000

出　　处：《中国免疫学杂志》2024年第2期288-292,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金面上项目(81373111);河北省卫健委资助项目(20190105)。

摘　　要：目的:探讨miR-150对小鼠外周T细胞PD-1表达及肺移植肿瘤生长的影响。方法:选取miR-150基因敲除(miR-150KO)及其野生型正常对照(WT)小鼠,流式细胞数术检测miR-150KO小鼠外周T细胞数量及其活化表型分子CD69和免疫检查点分子PD-1的表达变化;采用Lewis肺癌细胞系(LLC)皮下注射制备miR-150KO和WT小鼠移植肿瘤模型,观察miR-150敲除对肺肿瘤生长的影响;采用抗PD-1抗体腹腔注射miR-150KO和WT荷瘤小鼠,观察其对两组小鼠的肿瘤生长抑制效果。结果:与WT小鼠相比,miR-150KO小鼠脾脏和淋巴结CD4^(+)T细胞比例和数量显著升高,外周血CD4^(+)T和CD8^(+)T细胞比例和数量显著降低;miR-150敲除导致淋巴结和外周血CD4 T和CD8 T细胞中CD69^(+)细胞比例显著升高,同时导致外周血CD4 T和CD8 T细胞中PD-1^(+)细胞比例显著升高;与WT荷瘤小鼠相比,miR-150KO荷瘤小鼠肿瘤生长明显加快,同时miR-150KO荷瘤小鼠淋巴结和外周血CD4 T和CD8 T细胞中PD-1^(+)细胞所占比例显著升高。抗PD-1封闭抗体处理对miR-150KO荷瘤小鼠的肿瘤生长具有明显抑制作用。结论:miR-150敲除通过提高T细胞中PD-1表达促进小鼠肺肿瘤生长,同时增强抗PD-1抗体对肿瘤的免疫治疗作用。Objective:To investigate the effects of miR-150 on expression of PD-1 in peripheral T cells and lung tumor growth in mice.Methods:miR-150 gene knockout(miR-150KO)and wild-type normal control(WT)mice were selected,number changes of peripheral T cells,expression of activated phenotype molecule CD69,and immune checkpoint molecule PD-1 were detected by flow cytometry.Lewis lung cancer cell line(LLC)was used to prepare transplanted tumor models in miR-150KO and WT mice by subcuta-neous injection,and effect of miR-150 on growth of lung tumor was observed.Anti-PD-1 antibody was used to intraperitoneally inject miR-150KO and WT tumor-bearing mice,and its effect on tumor growth inhibition was observed.Results:Compared with WT mice,proportion and number of CD4^(+)T cells in lymph nodes and spleen of miR-150KO mice were significantly increased,while proportion and number of CD4^(+)T and CD8^(+)T cells in peripheral blood were significantly decreased.miR-150 knockout resulted in a significant increase in proportion of CD69^(+)cells in CD4 T and CD8 T cells of lymph nodes and peripheral blood,as well as a significant increase in proportion of PD-1^(+)cells in CD4 T and CD8 T cells of peripheral blood.Compared with WT tumor-bearing mice,tumor growth was significantly accelerated in miR-150KO tumor-bearing mice,and proportion of PD-1^(+)cells in CD4 T and CD8 T cells in peripheral blood and lymph nodes of miR-150KO tumor-bearing mice was also significantly increased.Anti-PD-1 antibody treatment significantly inhibited tumor growth of miR-150KO tumor-bearing mice.Conclusion:miR-150 knockout promotes the growth of transplanted lung tumor in mice by increasing expression of PD-1 in T cells,but also enhances the immunosuppressive effect of anti-PD-1 antibody on tumor.

关 键 词：miR-150 T细胞 肺肿瘤 PD-1 

分 类 号：R392.3[医药卫生—免疫学]