B7-H4在人子宫颈癌的表达及其与肿瘤内浸润T细胞亚群的相关性研究  

B7-H4 expression and it's correlation with the infiltrating T lymphocyte subtypes in human cervical cancers

作　　者：王婷婷[1] 徐曼[1] 耿卫朴[1] 黄文炼[1] 陈瑜[1] 

机构地区：[1]重庆医科大学病理教研室重庆医科大学分子与肿瘤研究中心,重庆400016

出　　处：《中国免疫学杂志》2012年第9期812-816,共5页Chinese Journal of Immunology

基　　金：重庆市自然科学基金(CSTC2009BB5268)项目

摘　　要：目的:研究共刺激分子B7-H4在人子宫颈癌的表达及其与肿瘤内浸润的FOXP3+、CD4+T、CD8+T细胞数量和分泌细胞因子的关系。方法:采用SP免疫组织化学染色检测B7-H4在30例正常人宫颈组织、30例高级别宫颈上皮内瘤变(Cervical intraepithelial neoplasiaⅡ-Ⅲ,CINⅡ-Ⅲ)和67例子宫颈癌的表达;间接免疫荧光双标(Indirect immunofluorescentdouble-staining)观察肿瘤内浸润的FOXP3+、CD4+T、CD8+T细胞数量及其TGF-β1和IFN-γ分泌情况。结果:B7-H4不表达于正常人宫颈上皮,仅在部分瘤变宫颈上皮微弱表达;子宫颈癌B7-H4的阳性表达率为46%(31/67),显著高于正常人宫颈上皮和瘤变宫颈上皮(P<0.01,P<0.05);子宫颈癌B7-H4阳性组病灶内浸润的CD8+T细胞以及分泌IFN-γ的CD8+T数量显著低于B7-H4阴性组(P<0.001,P<0.035);B7-H4的表达与肿瘤内浸润的FOXP3+细胞、CD4+T细胞以及分泌TGF-β1的CD4+T细胞数量无关(P>0.05,P>0.05)。结论:B7-H4在人子宫颈癌细胞异常高表达,并与肿瘤内浸润的CD8+T细胞数量减少以及分泌IFN-γ减少有关,提示B7-H4在抑制肿瘤微环境的细胞免疫中发挥作用。Objective：To investigate B7-H4 expression and it＇s correlation with the number of tumor-infiltrating FOXP3＋ lymphocytes,CD4＋T lymphocytes,CD8＋T lymphocytes and their cytokine secretion in human cervical cancers.Methods：B7-H4 expression was detected in 30 cases of normal human cervical tissue,30 cases of cervical intraepithelial neoplasia Ⅱ-Ⅲ（CINⅡ-Ⅲ）,and 67 cases of cervical cancer by immunohistochemistry SP staining.Tumor-infiltrating FOXP3＋,CD4＋T and CD8＋T lymphocytes,and the secretion of TGF-β1 and IFN-γ in cervical cancer tissues were detected by indirect immunofluorescent double-staining.Results：B7-H4 did not express in normal cervical tissue,but it faintly expressed in part epithelium of CINⅡ-Ⅲ,and expressed in 46%（31/67）cervical cancers.There was significant difference of B7-H4 expression between cervical cancers with normal cervical tissue and CINⅡ-Ⅲ（P0.01）.The number of tumor-infiltrating CD8＋T lymphocytes and their IFN-γ secretion in B7-H4 positive expression cervical cancers was significantly lower than that of B7-H4 negative cases（P0.001,P0.035）.There was no difference of tumor-infiltrating FOXP3＋ lymphocytes,CD4＋T lymphocytes and TGF-β1 secreting cells between B7-H4 positive cervical cancers with that of B7-H4 negative cases（P0.05,P0.05）.Conclusion：B7-H4 aberrantly expresses in human cervical cancers,and it is associates with decreasing tumor-infiltrating CD8＋T lymphocytes and their IFN-γ secretion.B7-H4 might play role on depressing anti-tumor T cell immune response in the microenvironment of cervical cancers.

关 键 词：B7-H4 FOXP3 CD4+T细胞 CD8+T细胞 TGF-β1 IFN-γ 子宫颈癌 免疫组织化学 免疫荧光 

分 类 号：R285.5[医药卫生—中药学]