基于肿瘤相关巨噬细胞的宫颈癌免疫学病理机制研究

Immunological pathology mechanism research of cervical cancer based on tumor related macrophage

目的:分析肿瘤相关巨噬细胞(TAMs)在宫颈癌发病中的作用机制,明确其与Th1/Th2比值、Th17/CD4^+CD25^+Foxp3^+Treg比值的相关性。方法:以27例宫颈癌患者和53例宫颈上皮内瘤变(CINⅡ22例、CINⅢ31例)患者为研究对象,治疗前抽取患者空腹肘静脉血,采用流式细胞仪测定Th1/Th2、Th17/CD4^+CD25^+Foxp3^+Treg比值,采用ELISA试剂盒测定血清IFN-γ、IL-4、IL-17A、IL-17F、TGF-β1、IL-10水平;术中留取病理组织,采用免疫组化实验测定TAMs CD68表达。结果:宫颈癌患者外周血Th1/Th2与Th17/CD4^+CD25^+Foxp3^+Treg比值低于CINⅢ,CINⅢ低于CINⅡ,各组之间的差异有统计学意义(P<0.05)。宫颈癌患者血清IL-4、TGF-β1、IL-10水平高于CINⅢ,CINⅢ高于CINⅡ,血清INF-γ、IL-17A、IL-17F水平低于CINⅢ,CINⅢ低于CINⅡ,各组之间的差异有统计学意义(P<0.05)。宫颈癌患者病灶组织TAMs CD68表达水平高于CINⅢ,CINⅢ高于CINⅡ,各组之间差异均有统计学意义(P<0.05)。相关性分析结果显示TAMs CD68表达水平与Th1/Th2比值、Th17/CD4^+CD25^+Foxp3^+Treg比值及IL-17A水平呈负相关性,与IL-10、IL-4水平呈正相关性(P<0.05)。结论:宫颈癌TAMs与Th1/Th2、Th17/CD4^+CD25^+Foxp3^+Treg密切相关,可能通过影响这两大体系的平衡介导宫颈癌的发生与发展。

AIM： To analyze the mechanism of tumor-associated macrophage（ TAMs） in the development of cervical cancer and to investigate its correlation with Th1/Th2 and Th17/CD4~＋CD25~＋Foxp3~＋Treg.METHODS： Twenty seven cases of cervical cancer and 53 cases of cervical intraepithelial neoplasias（ including 22 cases of CIN Ⅱ and 31 cases of CIN Ⅲ） were selected as subjects.The venous blood of patients before treatment was extracted to detect Th1/Th2 and Th17/CD4~＋CD25~＋Foxp3~＋Treg with flow cytometry,and detect serum IFN-γ,IL-4,IL-17 A,IL-17 F,TGF-β1 and IL-10 levels with ELISA Kits.Furthermore,pathological tissues were extracted during operation,and its TAMs CD68 expression was detected by immunohistochemistry technique.RESULTS： The Th1/Th2 and Th17/CD4~＋CD25~＋Foxp3~＋Treg of cervical cancer were both lower than those of CIN Ⅲ,and those of CIN Ⅲ were both lower than CINⅡ,the difference between groups had statistical significance（ P〈0.05）.The serum IFN-γ,IL-4,IL-17 A,IL-17 F,TGF-β1 and IL-10 levels of cervical cancer were all higher than those of CIN Ⅲ,and those of CIN Ⅲ were all higher than CINⅡ,the difference between groups had statistical significance（ P〈0.05）.The TAMs CD68 expression level of cervical cancer was higher than that of CIN Ⅲ,and that of CIN Ⅲ was lower than CINⅡ,the difference between groups had statistical significance（ P〈0.05）.The correlation analysis results showed TAMs CD68 expression level had negative correlations with Th1/Th2, Th17/CD4~＋CD25~＋Foxp3~＋Treg, and serum IL-17 A level,whereas presented positive correlations with serum IL-10 and IL-4 level（ P〈0.05）.CONCLUSION： TAMs is closely related with Th1/Th2 and Th17/CD4~＋CD25~＋Foxp3~＋Treg in cervical cancer,and possibly is mediating the occurrence and development of cervical cancer through influencing the balance of these two systems.