共刺激分子B7-H4在宫颈癌中的表达及意义

Expression of Costimulatory Molecule B7-H4 and Its Significance in Cervical Carcinoma

目的:肿瘤微环境中免疫共刺激分子B7-H4与其配体结合后可提供免疫抑制信号,调控肿瘤组织中的免疫应答。本研究探讨B7-H4、Fas及Caspase-3裂解片段在宫颈鳞状细胞癌中的表达及其与临床病理因素的关系,分析其参与肿瘤免疫逃逸的机制。方法:应用免疫组织化学SP法检测23例正常宫颈上皮、38例宫颈上皮内瘤变(CIN)和132例宫颈鳞状细胞癌组织中B7-H4、Fas及Caspase-3裂解片段的表达水平,分析其与宫颈癌各临床病理因素的相关性。结果:B7-H4在正常宫颈上皮组织中不表达,在CIN组织中微弱表达,在宫颈鳞状细胞癌组织中高表达。B7-H4表达与肿瘤的临床分期、淋巴结转移、原发肿瘤大小和肿瘤浸润深度有关,B7-H4与Fas蛋白表达呈现负相关,与Caspase-3裂解片段存在共表达关系。结论:B7-H4在宫颈鳞状细胞癌中过表达可引起Fas蛋白表达下调和Caspase-3裂解片段增多,抑制肿瘤细胞发生凋亡,参与肿瘤逃避宿主的免疫监视,从而促发宫颈癌的发生和发展。阻断B7-H4通路途径,有望成为宫颈鳞状细胞癌治疗的新靶点。

Objective：Immune costimulatory molecules B7-H4 binds with its ligand in the tumor micro-environment,which provides immune inhibitory signals,and further controls the immune response in tumor tissues.In this paper,we examined the expressions of B7-H4,Fas and Caspase-3 cleavage in cervical squamous cell carcinoma and tried to figure out their connections with it＇s clinical pathological factors to obtain the mechanism of tumor cell immune escape.Methods：Immunohistochemical method （SP） was applied to detect the expression levels ofB7-H4,Fas and Caspase-3 cleavage in 23 normal cases ofnomal cervical epithelium,38 cases of cervical intraepithelial neoplasia （CIN） and 132 cases of cervical squamous cancer cells,then analyzed its correlation with the clinicopathological factors in cervical cancer.Results：B7-H4 sshowed no expression in normal cervical epithelial tissues,showed weak expression in CIN tissues and high expression in cervical squamous cell carcinoma;B7-H4 expression was directly related to the clinical stage,lymph node metastasis,primary tumor size and depth of tumor invasion.B7-H4 showed negative correlation with the expression of Fas protein,and shared a co-expression with Caspase-3 cleavage.Conclusion：B7-H4 showing excessive expressions in cervical squamous cell carcinoma will lead to down-regulations of Fas protein expression and increasements of Caspase-3 cleavage.All these worked together induced tumor evading of host immune surveillance,thus inhibiting the apoptosis of tumor cells,which promotes the occurrence and deterioration of cervical cancer.Blocking the B7-H4 pathway is expected to become a new target in the treatment of cervical squamous cell carcinoma.