MUC1模拟表位肽致敏DC对宫颈癌荷瘤小鼠肿瘤生长及免疫微环境的影响  

Effects of MUC1 mimotope peptide sensitized DC on tumor growth and immune microenvironment in cervical cancer-bearing mice

作　　者：汪祖春 王烈宏[1] 祁青玲[1] WANG Zuchun;WANG Liehong;QI Qingling(Department of Gynecology,Qinghai Red Cross Hospital,Xining 810000,China)

机构地区：[1]青海红十字医院妇科,西宁810000

出　　处：《中国免疫学杂志》2023年第6期1285-1289,共5页Chinese Journal of Immunology

摘　　要：目的:研究黏蛋白1(MUC1)模拟表位肽致敏树突状细胞(DC)对宫颈癌荷瘤小鼠生长和免疫微环境的影响。方法:培养小鼠骨髓细胞,诱导并刺激DC成熟,MUC1模拟表位肽处理构建负载MUC1模拟表位肽的DC。构建稳定表达MUC1的宫颈癌U14细胞株的荷瘤BALB/c小鼠模型,随机分为3组:空白对照组(注射0.2 ml生理盐水)、DC组(注射2×10^(5)个未加MUC1模拟表位肽的DCs)和DC+MUC1组(注射2×10^(5)个负载MUC1模拟表位肽的DCs),免疫1周后进行二次免疫。治疗前和二次免疫1周后测量肿瘤体积;二次免疫1周后取小鼠肿瘤组织称重并计算抑瘤率;取小鼠外周血,流式细胞术检测CD3^(+)T、CD4^(+)T、CD8^(+)T细胞、CD4^(+)CD25^(+)Foxp^(3+)Treg水平;ELISA检测小鼠血清IL-6、IL-10、TGF-β、VEGF浓度。结果:与治疗前比较,空白对照组、DC组和DC+MUC1组肿瘤体积增大(P<0.05),治疗前各组差异无统计学意义(P>0.05),二次免疫1周后,DC+MUC1组肿瘤体积小于空白对照组和DC组(P<0.05),空白对照组和DC组差异无统计学意义(P>0.05);DC组和DC+MUC1组小鼠抑瘤率均高于空白对照组(P<0.05),DC+MUC1组小鼠抑瘤率高于DC组(P<0.05);DC+MUC1组小鼠外周血CD3^(+)T、CD4^(+)T、CD8^(+)T细胞水平高于空白对照组和DC组(P<0.05),空白对照组和DC组差异无统计学意义(P>0.05);DC+MUC1组CD4^(+)CD25^(+)Foxp^(3+)Treg和血清IL-6、IL-10、TGF-β、VEGF水平低于空白对照组和DC组,空白对照组和DC组差异无统计学意义(P>0.05)。结论:MUC1模拟表位肽致敏DC可抑制宫颈癌荷瘤小鼠肿瘤生长,改善肿瘤免疫微环境及细胞因子表达。Objective:To study effect of MUC1 mimotope peptide-sensitized dendritic cells(DC)on growth and immune microenvironment of cervical cancer-bearing mice.Methods:Mouse bone marrow cells were cultured to induce and stimulate DC maturation,and added MUC1 mimotope peptides to form DCs loaded with MUC1 mimotope peptides.Cervical cancer U14 cell line cancerbearing BALB/c mouse model was established,and randomly divided into 3 groups:blank control group(injected with 0.2 ml saline),DC group(injected with 2×10^(5)DC without MUC1 mimotope peptides)and DC+MUC1 group(injected with 2×10^(5)DCs with MUC1 mimotope peptides loaded).After 1 week of immunization,a second immunization was performed.Tumor volume before and 1 week after second immunization was measured.1 week after second immunization,tumor tissue was weighed and tumor inhibition rate was calculated.Peripheral blood of mice was taken and levels of CD3^(+)T,CD4^(+)T,CD8^(+)T cells,CD4^(+)CD25^(+)Foxp^(3+)Treg were measured by flow cytometry.Serum levels of IL-6,IL-10,TGF-βand VEGF were detected by ELISA.Results:Compared with before treatment,tumor volumes of blank control group,DC group and DC+MUC1 group were all increased(P<0.05),while there was no statistically significant difference between groups before treatment(P>0.05).1 week after second immunization,tumor volume of DC+MUC1 group was lower than blank control group and DC group(P<0.05),and there was no statistically significant difference between blank control group and DC group(P>0.05).Tumor suppression rate of mice in DC group and DC+MUC1 group were higher than in blank control group(P<0.05),and DC+MUC1 group was higher than DC group(P<0.05).Peripheral blood CD3^(+)T,CD4^(+)T,CD8^(+)T levels in DC+MUC1 group were higher than those in blank control group and DC group(P<0.05),and there was no statistically significant difference between blank control group and DC group(P>0.05).CD4^(+)CD25^(+)Foxp^(3+)Treg and serum IL-6,IL-10,TGF-β,VEGF levels in DC+MUC1 group were lower than those in blank control group and

关 键 词：黏蛋白1 模拟表位肽 树突状细胞 宫颈癌 免疫微环境 

分 类 号：R392[医药卫生—免疫学] R73-362[医药卫生—基础医学]