宫颈癌组织中FOXP^3+ Treg与PD-L1的表达情况及与临床特征的关系分析

Expression of FOXP3^+ Treg and PD-L1 in cervical cancer tissues and their relationship with clinical characteristics

目的分析宫颈癌组织中叉头框蛋白P3(FOXP3)+调节性T细胞(Treg)与程序性死亡受体配体1(PD-L1)的表达情况及与临床特征的关系。方法采用免疫组织化学SP法检测FOXP3+Treg、PD-L1蛋白在75例宫颈癌组织、38例宫颈上皮内瘤变(CIN)组织、30例正常宫颈组织中的表达情况,并分析宫颈癌组织中FOXP3+Treg、PD-L1蛋白表达情况与宫颈癌患者临床特征的关系,分析FOXP3+Treg、PD-L1蛋白表达情况的相关性,同时采用Cox回归分析法分析宫颈癌组织中FOXP3+Treg、PD-L1蛋白阳性表达的影响因素。结果FOXP3+Treg主要表达于肿瘤浸润淋巴细胞(TIL),PD-L1主要表达于宫颈癌细胞及TIL;宫颈癌组织中FOXP3+Treg、PD-L1蛋白阳性表达率均高于CIN组织、正常宫颈组织,CIN组织中FOXP3+Treg、PD-L1蛋白阳性表达率均高于正常宫颈组织,差异均有统计学意义(P﹤0.05)。FIGO分期为Ⅲ~Ⅳ期、低分化、有淋巴结转移的宫颈癌患者宫颈癌组织中FOXP3+Treg、PD-L1蛋白阳性表达率均高于FIGO分期为Ⅰ~Ⅱ期、中高分化、无淋巴结转移患者,差异均有统计学意义(P﹤0.05);而不同年龄、病灶大小及有无人乳头瘤病毒(HPV)感染的宫颈癌患者宫颈癌组织中FOXP3+Treg、PD-L1蛋白阳性表达率比较,差异均无统计学意义(P﹥0.05)。Spearman相关性分析发现,宫颈癌组织中FOXP3+Treg蛋白表达情况与PD-L1蛋白表达情况呈正相关(r=0.602,P﹤0.05)。FIGO分期为Ⅲ~Ⅳ期、低分化、有淋巴结转移为宫颈癌组织中FOXP3+Treg、PD-L1蛋白阳性表达的独立影响因素。结论免疫调节细胞FOXP3+Treg及相关免疫蛋白PD-L1在宫颈癌组织中高表达,可将其作为探索宫颈癌免疫治疗的新靶点。

Objective To analyze the expression levels of forkhead box P3 (FOXP3)+ regulatory T cells (Treg) and programmed cell death 1 ligand 1 (PD-L1) in cervical cancer tissues and their relationship with clinical characteristics. Method Immunofluorescence histochemical SP method was used to detect the expression levels of FOXP3+ Treg and PD-L1 protein in 75 cases of cervical cancer tissues, 38 cases of cervical intraepithelial neoplasia (CIN) tissues and 30 cases of normal cervical tissues. The relationship between expression levels of FOXP3+ Treg and PD-L1 protein and the clinical characteristics was analyzed, and the correlation between expression of FOXP3+ Treg and PD-L1 protein was also determined. Cox regression analysis was performed to analyze the factors influencing the positive expression of FOXP3+ Treg and PD-L1 in cervical cancer tissues. Result FOXP3+ Treg was mainly expressed in tumor infiltrating lymphocytes (TIL) while PD-L1 was mainly expressed in cervical cancer cells and TIL. The positive rates of FOXP3+ Treg and PD-L1 protein in cervical cancer tissues were higher than those in CIN tissues and normal cervical tissues (P<0.05), besides, they were also significant higher in CIN tissues compared to normal cervical tissues, showing statistical significance (P<0.05). The positive rates of FOXP3+ Treg and PD-L1 protein were higher in patients with FIGO stage III-IV, poorly differentiated disease and positive lymph node metastasis than in patients with FIGO stage I-II, moderately to highly differentiated disease and negative lymph node metastasis (P<0.05). No evident difference regarding the positive rates of FOXP3+ Treg and PD-L1 protein were noted among patients of different age, tumor sizes, and positive or negative human papilloma virus (HPV) infection (P>0.05). Spearman correlation indicated that, the expression of FOXP3+ Treg was positively correlated with PD-L1 protein expression in patients with cervical cancer (r=0.602, P<0.05). Cox regression analysis showed that, FIGO stage III-IV, poor differentiation and positive lymph node metastasis were factors influencing the positive expression of FOXP3+ Treg and PD-L1 protein in cervical cancer. Conclusion The expression of FOXP3+ Treg and PD-L1 are high in cervical cancer tissues, thus they may be employed as a novel target in the immunological treatment of cervical cancer.