NK细胞活化受体NKG2D及sMICA在晚期肺癌免疫监视中的作用

Role of NKG2D-Expressing NK Cells and sMICA in Immune Surveillance of Advanced Lung Cancer

背景与目的NK细胞活化受体NKG2D及sMICA是近来肿瘤研究领域热点之一。本研究旨在观察晚期肺癌患者外周血中NK细胞受体NKG2D及sMICA表达水平的变化,并探讨它们在晚期肺癌免疫监控中的作用及其临床意义。方法采用流式细胞术检测115例肺癌患者外周血NK细胞受体NKG2D、T淋巴细胞亚群及NK细胞百分比,采用酶联免疫吸附反应检测肺癌患者外周血sMICA值,并以50例健康人作为对照。结果晚期肺癌患者外周血sMICA、CD8+T细胞、NK细胞数量较对照组明显升高,而NK细胞受体NKG2D、CD3+T细胞、CD4+T细胞、CD4+T/CD8+T值较对照组下降。NK细胞受体NKG2D和sMICA呈负相关(r=-0.319,P<0.05)。NK细胞受体NKG2D与CD4+T细胞、CD4+T/CD8+T成正相关(P<0.05),与CD8+T细胞成负相关(P<0.05);sMICA与CD4+T细胞、CD4+T/CD8+T成负相关(P<0.05),与CD8+T细胞成正相关(P<0.05);它们与CD3+T、NK细胞均无相关性(P>0.05)。结论外周血sMICA上调介导NK细胞活化受体NKG2D下调机制参与了晚期肺癌以肿瘤为中心抑制免疫网络的形成,它们可作为监视晚期肺癌患者免疫状态的参考指标,也可作为评估肺癌发生、发展的参考依据。

Background and objective NKG2D-expressing NK cells and soluble major histoeompatibility complex class I -related chain A （sMICA） is one of aroused general interests in tumor research area recently. The aim of the study is to investigate the levels of NKG2D-expressing NK cells and sMICA in peripheral blood of advanced lung cancer which are remarkably related to clinical significance and analyse the role of NKG2D-expressing NK cells and sMICA in immune surveillance. Methods Flow cytometry was used to determine the percentage of NKG2D-expressing NK cells, T cell subsets, NK cells, and ELISA was used to mesure the levels of sMICA in peripheral blood of 115 advanced lung cancer patients and 50 healthy controls. Results Compared with control group, the levels of sMICA. CDS＋T cells, NK cells increased, while the levels of NKG2D-expressing NK cells, CD3^＋ T cells, CD4^＋ T cells, CD4^＋ T/CD8^＋ T in experimental group decreased. NKG2D-expressing NK cells had a perfect negative correlation with sMICA （r=-0.319, P〈0.05）. NKG2D-expressing NK cells had positive correlation with CD4^＋T cells, CD4^＋ T/CD8^＋T and negative correlation with CD8^＋T cells （P〈0.05）, sMICA had negative correlation with CD4^＋T cells, CD4^＋ T/CD8^＋ T and positive correlation with CD8^＋ T cells （P〈0.05）, they had no significant correlation with CD3^＋ T cells, NK cells respectively （P〈0.05）. Conclusion Accumulation of sMICA in serum may lead to the down-modulation of NKG2D-expressing NK which has been proposed to be a novel mechanism used by cancer cells to evade the tumor immunosurveillanee. They may be potential indicators investigating immune functions and helpful in the evaluation of their happening and proceeding.