细胞因子IL-33对肿瘤微环境的影响及其抗肿瘤作用

目的 探讨细胞因子IL-33对肿瘤微环境的影响及其抗肿瘤作用.方法 将70只小鼠分为对照组10只、干预组30只、模型组30只,其中干预组和模型组皮下接种H22细胞,造模饲养一周后干预组给予重组小鼠IL-33蛋白皮下注射,干预两周后比较小鼠肿瘤大小、血清IL-2、IL-4、IL-I0、IL-12p40、IFN-γ浓度、肿瘤微环境当中Th1型免疫应答以及瘤体OPN、TGF-β表达情况.结果 采用IL-33干预后,干预组小鼠肿瘤体积显著小于模型组,两组比较差异有统计学意义(P＜0.05).与对照组相比较,模型组IL-2、IL-12p40、IFN-γ显著降低(P＜0.05),IL-4显著升高(P＜0.05);干预组IL-2、IL-12p40、IFN-γ显著升高(P＜0.05),IL-4以及IL-10显著降低(P＜0.05);模型组与干预组各项血清指标比较差异有统计学意义(P＜0.05);干预组小鼠肿瘤肿瘤中浸润的CD45+免疫细胞百分比显著高于模型组小鼠(P＜0.05);干预组小鼠肿瘤肿瘤中浸润的CD45+免疫细胞百分比显著高于模型组小鼠(P＜0.05),且干预组小鼠肿瘤中CD8+T、NK细胞百分比均显著高于对照组(P＜0.05);干预组小鼠瘤体组织中OPN、TGF-β蛋白表达均较模型组有所降低.结论 细胞因子IL-33可明显抑制肿瘤的生长,调节肿瘤微环境中Th1/Th2免疫应答,且抑制肿瘤中TGF-β、OPN蛋白的表达,具有着潜的抗肿瘤作用,为肿瘤的免疫治疗提供了新的方向.

The influence of IL-33 on tumor microenvironment and its anti tumor effect

Objective To investigate the effect of IL-33 on tumor microenvironment and its antitumor effect.Methods 70 mice were randomly divided into control group (10 mice),intervention group (30 mice),model group (30 mice).Intervention group and model group were treated with H22 cells,and IL-33 protein was injected subcutaneously in intervention group after one week.After two weeks,the tumor size of mice,serum levels of IL-2,IL-4,IL-10,IL-12p40,IFN-γ,Thl type immune response in tumor microenvironment,and the expression of OPN and TGF-β in tumor cells were compared.Results After IL-33 intervention,the tumor volume of intervention group was significantly less than that of model group,with statistically significant difference between two groups (P＜0.05).Compared with control group,IL-2,IL-12p40,IFN-γ in model group decreased significantly (P＜0.05),IL-4 increased significantly (P＜0.05);IL-2,IL-12p40,IFN-γ in intervention group increased significantly (P＜0.05),IL-4,IL-10 decreased significantly (P＜0.05),with statistically significant differences between intervention group and model group (P＜0.05).The percentage of CD45+ immune cells in the tumor of intervention group was significantly higher than that of model group,control group (P＜0.05).The percentage of NK and CD8+T immune cells in the tumor of intervention group were significantly higher than those of control group (P＜0.05).The expression of OPN and TGF-β in the tumor tissues in intervention group were lower than those in model group.Conclusions IL-33 can significantly inhibit tumor growth,adjust Th1/ Th2 immune response in tumor microenvironment,and inhibit the expression of OPN and TGF-β protein in tumor cells,which has a potential anti-rumor effect,and provides a new direction for tumor immunotherapy.