CD4^+ CD25^+调节性T细胞及Foxp3基因在不同淋巴结转移状态的非小细胞肺癌患者中的表达差异

The difference of CD4^+ CD25^+ regulatory T cells and Foxp3 expression in non-small cell lung cancer patients with different lymph node metastasis status

目的:比较CD4+CD25+调节性T细胞及Foxp3基因在不同淋巴结转移状态的非小细胞肺癌患者外周血及肿瘤微环境中的表达差异。方法:46例初诊、初治的非小细胞肺癌患者根据有无淋巴结转移分为两组,采用流式细胞仪检测两组患者外周血中CD4+CD25+调节性T细胞的比例,Real-time PCR检测Foxp3基因的表达,免疫组化法检测肿瘤微环境中Foxp3的表达情况,ELISA法检测外周血及肿瘤组织匀浆中的TGF-β和IFN-γ水平。结果:Foxp3基因在转移淋巴结中的表达明显强于无转移的淋巴结,有淋巴结转移的非小细胞肺癌患者肿瘤微环境中的Foxp3表达明显强于无淋巴结转移的非小细胞肺癌患者,前者肿瘤组织匀浆中的TGF-β水平也明显高于后者,差异均具有显著性。两组患者外周血中CD4+CD25+调节性T细胞比例、Foxp3基因的表达及TGF-β、IFN-γ水平比较无显著性差异。结论:有淋巴结转移的非小细胞肺癌患者肿瘤微环境中存在Foxp3基因表达增强及TGF-β水平增高的现象,提示该类患者存在较为严重的局部肿瘤免疫抑制状态。

Objective：To compare the difference of CID4＋ CD25 ＋ regulatory T cells and Foxp3 expression in the periphery blood and tumor microenvironment of non-small cell lung cancer （NSCLC） patients with different lymph node metastasis status. Methods ：46 NSCLC patients were divided into two groups according to their lymph node metastasis status. The proportion of CD4 ＋ CD25＋ T cells was analyzed by flow cytometry, the mRNA expression of Foxp3 was detected by real-time PCR and immunohistochemistry was ap- plied for detecting Foxp3 expression in tumor microenvironment. The levels of TGF-18 and IFN-3, in periphery blood and tumor homogenares of patients were tested by ELISA. Results： Foxp3 expression in the metastatic lymph nodes was stronger than that in the non-meta- static ones of NSCLC patients. Foxp3 expression in the tumor microenvironment as well as the levels of TGF-β in tumor homogenates of NSCLC patients with metastatic lymph nodes were all higher than those in patients with non-metastatic ones. There was no significant difference in the proportion of CD4＋ CD25 ＋ T. cells, Foxp3 expression and levels of TGF-13 and IFN-γ in the periphery blood of two group patients. Coneiusion：Foxp3 expression in the tumor microenvironment and TGF-13 level in tumor homogenates of NSCLC patients with metastatic lymph nodes were higher than those of patients with non-metastatic ones, which suggested more serious local immunosuppression situation in this kind of NSCLC patients.