共刺激分子PD-L1、PD-L2和B7-H4在人子宫颈癌的表达及意义

An investigation of PD-L1,PD-L2 and B7-H4 expressions in human cervical cancer and their significance

目的：研究共刺激分子程序性死亡配体1（Programmed death ligand 1,PD-L1）、程序性死亡配体2（Programmeddeath ligand 2,PD-L2）和B7-H4在人子宫颈癌的表达及其与临床病理特征的关系。方法：采用免疫组织化学PV-6000法检测PD-L1、PD-L2和B7-H4在10例正常人宫颈组织、10例高级别CIN（CINⅡ~Ⅲ级）和67例子宫颈癌中的表达,并分析3种共刺激分子的表达与子宫颈患者临床病理特征的相关性。结果：正常人宫颈组织上皮不表达PD-L1和B7-H4,而基底层细胞微弱表达PD-L2;CINⅡ~Ⅲ的瘤变宫颈上皮微弱表达PD-L1、PD-L2和B7-H4;子宫颈癌细胞表达PD-L1、PD-L2和B7-H4的阳性率分别为70%（47/67）、51%（34/67）和46%（31/67）。统计学分析显示宫颈癌细胞PD-L1的表达与癌细胞浸润深度明显相关（P〈0.01）,与年龄、组织学类型无关;PD-L2的表达与肿瘤的淋巴结转移（P〈0.05）有关;B7-H4的表达与肿瘤的淋巴结转移（P〈0.05）和局部血管内瘤栓形成（P〈0.05）相关。结论：人子宫颈癌细胞异常表达PD-L1、PD-L2和B7-H4,且与肿瘤浸润和转移密切相关。PD-L1、PD-L2和B7-H4可能成为子宫颈癌免疫治疗的潜在靶点。

Objective：To investigate the expressions of co-stimulation molecules PD-L1,PD-L2 and B7-H4 in human cervical cancers and their association with clinical and pathologic characteristics of the patients.Methods：The expressions of PD-L1,PD-L2 and B7-H4 in 10 cases of normal human cervical tissue,10 cases of CINⅡ~Ⅲ,and 67 cases of cervical cancer were detected by immunohistochemistry PV-6000 staining,and the relationship of their expressions to clinical and pathologic characteristics was evaluated.Results：There was no PD-L1 or B7-H4 expression in normal cervical tissue,but weak expression of PD-L2 in basal cervical epithelium;faint expressions of PD-L1,PD-L2 and B7-H4 were determined in CINⅡ~Ⅲ;70%（47/67）PD-L1,51%（34/67）PD-L2 and 46%（31/67）B7-H4 were detected in cervical cancers.PD-L1 expression in cancer cells was related to the cancer invasion depth（P0.01）,PD-L2 expression related to the lymph node metastasis（P〈0.05）,and B7-H4 expression related to lymph node metastasis（P〈0.05）and vascular invasion（P〈0.05）.Conclusion：PD-L1,PD-L2 and B7-H4 express aberrantly in cervical cancer and are closely associated with the invasion and metastasis of cervical cancer.PD-L1,PD-L2 and B7-H4 may be the potential immunotherapy targets of cervical cancer.