髓源性抑制细胞在靶向肝再生磷酸酶-3小鼠乳腺肿瘤基因免疫中的表达  

Expression of myeloid-derived suppressor cells in targeted phosphatase of regeneratiing liver-3 mouse breast tumor gene immunity

作　　者：吕娟[1] 黄昊 赵燕田[1] LYU Juan;HUANG Hao;ZHAO Yantian(Department of Clinical Laboratory,Beijing Chaoyang Hospital Affiliated to Capital Medical University,Beijing100020,China;Key Laboratory of Carcinogenesis and Translational Research,Department of Biochemistry and Molecular Biology,Peking University Cancer Hospital&Institute,Beijing100142,China)

机构地区：[1]首都医科大学附属北京朝阳医院检验科,北京100020 [2]北京大学临床肿瘤学院北京大学肿瘤医院暨北京市肿瘤防治研究所生物化学与分子生物学研究室恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处：《中国医药导报》2020年第26期79-85,103,共8页China Medical Herald

基　　金：国家自然科学基金青年科学基金项目(81301796);北京市自然科学基金青年科学基金项目(7144213);北京市医院管理中心“青苗”计划专项经费资助项目(QML20150304)。

摘　　要：目的观察髓源性抑制细胞(MDSC)在靶向肝再生磷酸酶-3(PRL-3)小鼠乳腺肿瘤基因免疫中的表达,探讨MDSC的数量与肿瘤生长的关系。方法将40只雌性BALB/c小鼠分为5大组(8小组),空载对照组[pVAX1(-)组]、无佐剂组PRL-3组(K-PRL3组)、佐剂-PRL-3融合蛋白组(K-T-PRL3组和K-PRL3-MT组)及MDSC对照抗体删除组(K-T-PRL3+Ab control组和K-PRL3-MT+Ab control组),MDSC特异性抗体删除组(K-T-PRL3+Gr-1Ab组和K-PRL3-MT+Gr-1 Ab组),通过流式细胞术检测免疫表型CD45、Gr-1及CD11b,分析MDSC在各免疫组外周血、肿瘤、脾脏中的表达水平,观察MDSC与肿瘤生长的相关性。结果荷瘤后第28天K-PRL3组、K-T-PRL3组和K-PRL3-MT组肿瘤体积均小于pVAX1(-)组,差异均有统计学意义(均P<0.05);K-PRL3-MT组和K-T-PRL3组与K-PRL3组肿瘤体积比较,差异无统计学意义(P>0.05)。佐剂-PRL-3融合蛋白组小鼠外周血或肿瘤组织中MDSC表达均高于K-PRL3组,差异有统计学意义(P<0.05)。MDSC特异性抗体删除组(K-T-PRL3+Gr-1 Ab组和K-PRL3-MT+Gr-1 Ab组)与MDSC对照抗体删除组(K-T-PRL3+Ab control组和K-PRL3-MT+Ab control组)肿瘤体积大小比较,差异无统计学意义(P>0.05);MDSC特异性抗体删除组、MDSC对照抗体删除组肿瘤体积均大于无佐剂组PRL-3组和佐剂-PRL-3融合蛋白组,差异有统计学意义(P<0.01);MDSC特异性抗体删除组脾脏、外周血MDSC表达均低于对照抗体删除组,而肿瘤组织中MDSC表达与MDSC对照抗体删除组比较,差异无统计学意义(P>0.05),且均大于佐剂-PRL-3融合蛋白组,差异有统计学意义(P<0.01)。结论在靶向PRL-3的小鼠乳腺肿瘤基因免疫中佐剂-PRL-3融合蛋白组肿瘤组织中MDSC与肿瘤生长相关,为进一步优化靶向PRL-3的抗肿瘤免疫治疗方案及MDSC相关作用研究提供理论依据。Objective To observe the expression of myeloid suppressor cells(MDSC)in targeted phosphatase of regeneratiing liver-3(PRL-3)mouse breast tumor gene immunity,and to explore the relationship between the number of MDSC and tumor growth.Methods Forty female BALB/c mice were divided into five groups(eight groups):no-load control group(pVAX1[-]group),adjuvanted PRL-3 group(K-PRL3 group),adjuvanted PRL-3 fusion protein group(K-T-PRL3 group and K-PRL3-MT group),and MDSC control antibody deletion group(K-T-PRL3+Ab control group and K-PRL3-MT+Ab control group).In the MDSC specific antibody deletion group(K-T-PRL3+GR-1AB group and K-PRL3-MT+GR-1 Ab group),immunophenotypes CD45,GR-1 and CD11b were detected by flow cytometry to analyze the expression levels of MDSC in peripheral blood,tumor and spleen of each immune group,and the correlation between MDSC and tumor growth was observed.Results On the 28th day after tumor-bearing,the tumor volume of K-PRL3 group,K-T-PRL3 group and K-PRL3-MT group was all smaller than pVAX1(-)group,with statistically significant differences(all P<0.05).There was no significant difference in tumor volume between the K-PRL3-mt group and K-T-PRL3 group and K-PRL3 group(P>0.05).The expression of MDSC in peripheral blood or tumor tissues of the adjuvant-PRL-3 fusion protein group was higher than that of the K-PRL3 group,and the difference was statistically significant(P<0.05).There was no significant difference in tumor volume between MDSC specific antibody deletion group(K-T-PRL3+GR-1 Ab group and K-PRL3-mL+GR-1 Ab group)and MDSC Control group(K-T-PRL3+Ab control group and K-PRL3-MT+Ab control group)(P>0.05).The tumor volume of the MDSC specific antibody deletion group and the MDSC control antibody deletion group were all larger than those of the adjuvant-free PRL-3 group and the adjuvant-PRL-3 fusion protein group,with statistically significant differences(P<0.01).The expression of MDSC in spleen and peripheral blood of the MDSC specific antibody deletion group was lower than that of the control ant

关 键 词：髓源性抑制细胞 肝再生磷酸酶-3 肿瘤免疫抑制微环境 流式细胞术 

分 类 号：R735.9[医药卫生—肿瘤]