CD8^+NKT细胞表面活化性受体NKG2D在肺癌患者外周血中的表达及临床意义

Expression and Clinical Significance of CD8^+Natural Killer T Cell Stimulatory Receptor NKG2D in Peripheral Blood of Lung Cancer Patients

背景与目的 NKT细胞活化性受体NKG2D及sMICA是近来肿瘤免疫研究领域的热点之一。本研究旨在观察肺癌患者外周血中CD8+NKT细胞受体NKG2D表达水平的变化,并对NKG2D及sMICA进行相关性分析,探讨它们在肺癌免疫监视中的作用及临床意义。方法选择82例初发未治疗的肺癌患者,采用流式细胞术检测外周血CD8+NKT细胞活化性受体NKG2D的表达,并以45例健康人作对照,采用酶联免疫吸附法检测肺癌患者血清中sMICA的表达,分析NKG2D与肺癌临床生物学特征的关系。结果肺癌患者外周血中CD8+NKT细胞表面活化性受体NKG2D水平均低于对照组,差异有统计学意义(P<0.001)。随TNM分期的增加,NKG2D的表达率逐渐降低。其中IV期肺癌患者NKG2D的表达明显低于I期-II期及III期患者该受体的表达,差异有统计学意义(P<0.001)。肺Ca患者中吸烟人群外周血中CD8+NKT细胞受体NKG2D的表达较非吸烟者低,差异有统计学意义(P<0.05)。CD8+NKT细胞受体NKG2D与sMICA呈负相关(r=-0.598,P<0.001)。结论肺癌患者CD8+NKT细胞表面受体NKG2D在外周血中低表达,且与肺癌的分期有关;该受体的下调通过血清中sMICA上调的机制参与了肺癌以肿瘤为中心抑制免疫网络的形成;监测NKG2D及sMICA有助于了解患者的免疫功能,可为临床肿瘤的综合治疗提供依据。

Background and objective NKG2D-expressing CD8^＋NKT cells and soluble major histocompatibility complex class I-related chain A （sMICA） is one of recently emerged general interests in tumor research area. The aim of this study is to investigate the levels of NKG2D-expressing CD8^＋NKT cells in peripheral blood of lung cancer patients, which are remarkably related to clinical significance, and to analyze the correlation between NKG2D-expressing CD8^＋NKT cells and sMICA levels, and to explore the role of NKG2D and sMICA in immune surveillance. Methods Flow cytometry was used to determine the percentage of NKG2D-expressing CD8^＋NKT cells, and ELISA was used to measure the levels of sMICA in peripheral blood of 82 untreated lung cancer patients and 45 healthy controls. The association of NKG2D levels with clinical fea-tures was analyzed. Results The expression of NKG2D on CD8^＋NKT cells in lung cancer group was significantly lower than that in healthy group, with statistically significant difference （P〈0.001）. And with the increase of TNM stage, NKG2D expression rate reduced gradually. NKG2D expression in stage IV disease was significantly lower than which stage I-II and III disease （P〈0.001）. The expression of NKG2D on CD8^＋NKT cells was remarkably lower in that in smokers than that in non-smokers, with statistically significant difference （P〈0.05）. NKG2D exhibited negative correlation with sMICA （r=-0.598, P〈0.001）. Conclusion Lung cancer has low expression of NKG2D in CD8^＋NKT cells which correlate with pathological stage. Detection of NKG2D and sMICA might be helpful to understand immune functions and provide evaluation of combined treatment for clinical cancer.