可溶性MICA在乳腺癌免疫逃逸中的作用

The roles of soluble MICA in immune escape of breast tumor

目的:观察乳腺癌患者血清中可溶性MICA(sMI-CA)表达情况,探讨sMICA在乳腺癌免疫逃逸中的作用。方法:ELISA方法检测乳腺肿瘤患者外周血sMICA的分泌。流式细胞术(FCM)检测sMICA及白细胞介素15(IL-15)对NK细胞表面NKG2D表达的影响。MTT法检测NK细胞对乳腺癌细胞的杀伤活性。结果:ELISA结果显示,血清sMICA含量在健康成年人血清中为阴性,在乳腺良性肿瘤患者血清中含量为(76.8±22.3)ng/L,在恶性肿瘤患者血清中含量为(205.36±71.27)ng/L,乳腺癌患者中血清sMICA含量高低与TNM分期呈正相关。应用含sMICA的血清与NK细胞共培养可明显下调NK细胞的杀瘤活性[(76.2±6.7)%vs(48.4±4.1)%],NK细胞表面NKG2D表达和上清中IFN-γ分泌量也下降。IL-15明显上调NK细胞表面NKG2D表达,增加培养上清IFN-γ分泌量和增强NK对MCF-7的杀瘤活性。结论:sMICA表达与乳腺癌TNM分期正相关,sMICA通过下调NK细胞NKG2D表达水平而降低NK细胞杀瘤活性,在肿瘤免疫逃逸中起重要作用。IL-15可以上调NK细胞NKG2D的表达并增强NK细胞杀瘤活性。

AIM; To determine the expression of soluble MICA （sMICA） in serum of patients with breast tumor, and explore the roles of sMICA in immune escape. METHODS： ELISA was used to examine the sMICA in peripheral blood. The expression of NKG2D were identified by Flow cytometry. The cytotoxicity of NK cells to breast cancer cells was observed with MTT assay. RESULTS： sMICA was not detected in the serum of healthy person, but （76.8 ± 22.3 ） ng/L in breast benign tumor patients and（205.4 ±71.3）ng/L in breast malignant tumor patients. There was positive correlation between sMICA levels and breast cancer stage. After incubation with sMICA, NK cells got decrease in cytotoxicity from（76.2 ±6.7）% to （48.4±4. 1 ）% . The expression of NKG2D and secretion of IFN-γ decreased at the same time. IL-15 up-regulated the expression of NKG2D on NK cells and increased NK cells cytotoxicity to breast cancer cells. CONCLUSION： sMICA level is positive correlated with breast cancer TNM stage, sMICA reduced the expression of NKG2D, impaired NK-mediated immune surveillance and led to immune escape of breast tumor. IL-15 could upregulate the expression of NKG2D and increase NK cells cytotoxicity.