结肠癌患者单核或树突状细胞MICA的表达及其与NK细胞活性的关联

摘要

Objechve :To observe whether MHC class Ⅰ chain-related protein A (MICA ) is expressed on monocytes or dendritic cells (DCs) and to study the correlation between frequency of MICA+ monocytes with activities of natural killer (NK ) cells from peripheral blood of colorectal cancer patients .Methods :Firstly ,MICA expression on monocytes or monocyte-derived dendirtic cells was detected by flow cytometry (FCM ) .Variation of MICA expression was analyzed on dendritic cells both before and after stimulations with IL-15 or IFN-α .Then the frequencies of NKG2D+ ,CD16+ ,CD69+NK cells and cytotoxicities of NK cells were detected by FCM .Lastly ,the correlation of MICA+ monocyte frequency with NK cell activities was statistically analyzed .Results :Compared with that of healthy controls ,there was not significantly difference of MICA expression on monocytes in caner patients .MICA expression was detected on immature DCs .MICA expression level on DCs was ont enhanced after DCs were stimulated with IL-15 or IFN-α in colorectal cancer patients .Frequencies of NKG2D+ or CD69+ NK cells and cytotoxicity of NK cells were decreased in cancer patients ,whereas frequency of CD16+ NK cells was similar in both groups .There was not significantly correlation between the frequency of MICA+ monocytes and the frequency of NKG2D + NK cells .However in colorectal patients ,frequency of MICA+ monocytes was positively correlated with frequency of CD 107a positive NK cells ,which was induced in the co-cultured with target cells in colorectal cancer patients .Conclusion :In colorectal cancer patients ,MICA expression on monocytes is not related with NKG 2D expression on NK cells ,but higher frequencies of MICA positive monocytes are associated with higher cvtotoxicitv of NK cells .%目的:观察结肠癌患者单核或树突状细胞是否表达MHC Ⅰ类相关抗原A(MICA),并分析MICA+单核细胞的频率是否与患者体内NK细胞的活性相关联.方法:首先利用流式细胞仪检测MICA在外周血单核细胞和由单核细胞诱导而来树突状细胞(DCs)上的表达;并用IL-15和IFN-α刺激树突状细胞,观察MICA表达的变化;然后检测患者外周血NKG2D+、CD16+、CD69+NK细胞的频率及NK细胞的杀伤活性;最后分析MICA+单核细胞的频率是否与NK细胞表达NKG2D及其杀伤活性关联.结果:与健康个体相比,结肠癌患者MICA+单核细胞的频率无显著变化.未成熟DCs表达MICA,但受IL-15和IFN-α刺激后,结肠癌来源的DCs表面MICA的表达无显著上调.结肠癌患者外周血NKG2D+、CD69+NK细胞的频率显著降低,NK细胞的杀伤活性显著降低,而CD16+NK细胞的频率无明显变化.结肠癌患者MICA+单核细胞的频率与NK细胞表达NKG2D无明显关联,但与NK细胞杀伤靶细胞时CD107a的表达正相关.结论:结肠癌患者体内单核细胞表达MICA与NK细胞表达NKG2D无关,但高频率MICA阳性的单核细胞与NK细胞的抗肿瘤活性正相关.