程序性死亡分子1及其配体在口腔鳞状细胞癌患者外周血中的表达及临床意义

Levels of programmed death-1 and programmed death ligand-1 in the peripheral blood of patients with oral squamous cell carcinoma and its clinical implications

目的检测口腔鳞状细胞癌患者外周血中程序性死亡分子1(PD-1)及其配体(PD-L1)的表达水平,探讨其生物学及临床意义。方法选取82例口腔鳞状细胞癌患者(口腔鳞癌组)和25例健康对照者(对照组)为研究对象,收集研究对象的外周血,采用流式细胞术检测外周血T淋巴细胞表面PD-1、PD-L1的表达及T淋巴细胞亚群计数,采用酶联免疫吸附方法检测血清中可溶性PD-1(s PD-1)和可溶性PD-L1(s PD-L1)的表达水平。采用SPSS 17.0软件对数据进行检验和相关性分析。结果口腔鳞癌组外周血CD8+T淋巴细胞百分数明显高于对照组(P<0.05),而CD3+、CD4+T淋巴细胞百分数及CD4+/CD8+T亚群百分数比值均低于对照组(P<0.05)。口腔鳞癌组外周血CD4+、CD8+T淋巴细胞表面PD-1、PD-L1的阳性表达率均高于对照组(P<0.01)。口腔鳞癌组血清s PD-L1水平高于对照组(P<0.05),而s PD-1水平二者差异无统计学意义(P>0.05)。s PD-L1的表达与临床分期、肿瘤分化程度及淋巴结转移状态相关(P<0.05),与性别、年龄、肿瘤部位及大小无关。结论口腔鳞状细胞癌患者外周血T淋巴细胞亚群存在不同程度的免疫功能抑制,CD4+和CD8+T淋巴细胞表面PD-1及PD-L1表达显著升高。异常升高的s PD-L1可能与口腔鳞状细胞癌的发生发展有关。

Objective To detect the expression levels of programmed death-1 （PD-1） and programmed death ligand-1 （PD-L1） in the peripheral blood of patients with oral squamous cell carcinoma （OSCC） and to discuss their biological and clinical significance. Methods PD-1/PD-L1 expression on the surface of T-lymphocytes and the counts of T-lymphocyte subpopulations of peripheral blood in 82 patients with OSCC （OSCC group） and 25 healthy controls （control group） were examined via flow cytometry. The expression levels of soluble PD-1 （sPD-1） and soluble PD-L1 （sPD-L1） in the serum were observed through enzyme-link immunology method. The data were tested and analyzed with SPSS 17.0 software. Results The percentage of CD8＋ T cells in the OSCC group was significantly higher than that in the control group （P〈0.05）, whereas the percentages of CD3＋ and CD4＋ T cells as well as CD4＋/CD8＋ ratio were significantly lower than those in the control group （P〈0.05）. The positive rates of PD-1 and PD-L1 in CD3＋ and CD4＋ T cells in OSCC peripheral blood were remarkably higher than those in the control group （P〈0.01）. Difference was not observed between the expression levels of sPD-1 in the serum of OSCC group and those in the control group （P〉0.05）, but the average of sPD-L1 was remarkably higher than that in the control group （P〈0.05）. sPD-L1 expression was related to clinical stage, tumor cell differentiation, and lymph node status （P〈0.05） but not related to sex, age, tumor location, and tumor size. Conclusion T-lymphocyte subpopulations in the peripheral blood of patients with OSCC developed immunosuppression with different degrees. PD-1 and PD-L1 expression levels on the surface of CD3＋ and CD4＋ T cells significantly increased. Abnormal increase in sPD-L1 expression may be associated with OSCC development.