B7家族及其受体PD-1在人NK/T细胞淋巴瘤中的表达及临床意义

The expression and clinical significance of B7 family molecules and their receptor PD-1 in human NK/T-cell lymphoma

目的:探讨B7家族及其受体(programmed death-1,PD-1)在人NK/T细胞淋巴瘤(NKTL)中的表达及临床意义。方法:荧光定量PCR(real time fluorescence quantitative PCR,RQ-PCR)及免疫组织化学SP法检测PD-1及B7家族PD-L1、PD-L2在人NKTL细胞系(SNK-6、YTS)及NKTL组织中的表达,并分析其与临床病理学参数及临床疗效之间的关系。结果:PD-L1和PD-L2mRNA在SNK-6、YTS中的表达明显高于正常NK细胞。PD-L1和PD-L2蛋白在NKTL组织中的表达阳性率(分别为60.0%、63.3%)明显高于鼻炎组织(22.2%、16.7%);NKTL组织中PD-1+肿瘤浸润T淋巴细胞(TIL)数与PD-L1、PD-L2的表达均呈负相关;PD-L1和PD-L2的表达水平与分期均呈正相关,PD-L1与LDH、Ki-67水平呈正相关,PD-L1与IPI评分呈负相关,PD-L1及PD-L2与其他临床病理学参数无显著相关性。PD-L1与治疗疗效呈负相关,而PD-L2与治疗疗效无明显相关性。结论:B7家族及其受体PD-1在人NKTL中高表达且具有一定的临床意义,PD-L/PD-1信号途径可能参与了NKTL的免疫逃逸,有望成为人NK-TL免疫治疗的新靶点。

Objective： To investigate the expression and clinical significance of B7 family molecules and their receptor PD-1（ programmed death-l） in human NK/T-cell lymphoma （NKTL）. Methods： Real time fluorescence quantitative PCR （RQ-PCR） and Immunohistochemistry SP method were used to detect the expression levels of PD-1 and B7 family molecules （PD-L1 and PD-L2） in human NKTL cell lines （SNK-6 and YTS） and NKTL tissues .The correlation between these proteins and Clinical histopathological parameters and curative effect were analyzed subsequently. Results： The expression levels of PD-L1 and PD-L2 mRNA in SNK-6 and YTS were significantly higher than that in normal NK cells.. The expression of PD-L1 and PD-L2 proteins in human NKTL tissues （60.0%, 63.3%） and curative effect were significantly increased compared with rhinitis tissues （22.2%, 16.7%）;furthermore, the mean count of PD-1 ＋Tumor-infiltrating T lymphocytes（TIL） was inversely correlated with PD-L1 and PD-L2 protein expression levels in NKTL tissues.. The expression of PD-L1 and PD-L2 showed a positive correlation with clinical stage.. PD-L1 expression was also positively correlated with LDH, Ki-67 level and was negatively correlated with IPI score. However, there were no significant correlation between PD-L1 and PD-L2 with other Clinical histopathological parameters..-PD-L1 expression was negatively correlated with curative effect. However, there was no correlation between PD-L2 expression and curative effect. Conclusion： B7 family molecules and their receptor PD-1 are overexpressed in human NKTL and have greatly clinical significance.PD-L/PD-1 pathway may involved in the tumor immune escape in human NKTL, and it is expected to be a novel target for immunotherapy of human NKTL.