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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: B7-H4, an immunostimulatory molecule in tumor microenvironment, binds to its ligand to provide immunosuppressive signal and regulate immune response in tumor tissue. This study was to investigate the expression of B7-H4, Fas and Caspase-3 cleavage fragments in cervical squamous cell carcinoma and its relationship with clinicopathological factors, and to analyze its mechanism involved in tumor immune escape. Methods: The expressions of B7-H4, Fas and Caspase-3 cleavage fragments in 23 cases of normal cervical epithelium, 38 cases of cervical intraepithelial neoplasia (CIN) and 132 cases of cervical squamous cell carcinoma were detected by immunohistochemical SP method. Analyze its correlation with clinicopathological factors of cervical cancer. Results: B7-H4 was not expressed in normal cervical epithelium, weakly expressed in CIN tissues and highly expressed in cervical squamous cell carcinoma tissues. The expression of B7-H4 was correlated with the clinical stage, lymph node metastasis, the size of primary tumor and the depth of tumor invasion. The expression of B7-H4 was negatively correlated with the expression of Fas protein and co-expressed with the fragment of Caspase-3. Conclusion: Overexpression of B7-H4 in cervical squamous cell carcinoma can result in the down-regulation of Fas protein and the increase of the fragment of Caspase-3, inhibiting the apoptosis of tumor cells and participating in the immune surveillance of tumor escape host to promote the occurrence of cervical cancer And development. Blocking the B7-H4 pathway, is expected to become a new target for the treatment of cervical squamous cell carcinoma.