非小细胞性肺癌病人相关细胞因子的表达

THE EXPRESSION OF CYTOKINE mRNA IN NON-SMALL CELL LUNG CANCER

目的探讨非小细胞性肺癌(NSCLC)病人局部微环境中免疫反应特点及其对抗肿瘤免疫的影响。方法以5例结核性胸膜炎病人作为对照,采用地高辛末端标记的寡核苷酸探针,以原位杂交技术检测了23例NSCLC病人的新鲜胸腔积液和(或)手术切除标本淋巴细胞和肿瘤细胞中IL-2、INF-γ、IL-4、IL-10、TGF-β1、IL-1、IL-3I、L-8、GM-CSF、TNF-α及TGF-αmRNA的表达。结果病人胸腔积液的单个核细胞及肿瘤组织中,IL-4、IL-10、TGF-α和TGF-β1 mRNA的表达水平明显高于IL-2I、L-12、IL-18、INF-γ;而结核性胸腔积液的单个核细胞中上述细胞因子的水平均降低,并且各细胞因子的表达水平之间没有明显的差异。结论NSCLC病人胸腔积液的单个核细胞及肿瘤组织中,Ⅱ型细胞因子和免疫抑制细胞因子mRNA的表达占主导地位,反映了肿瘤局部的免疫微环境处于抑制状态。上述结果有助于了解肿瘤逃逸的机制,并为制定NSCLC免疫治疗的方案提供了重要的实验依据。

Objective To explore the characteristics of immune responses in the microenvironment of non-small cell lung cancer （NSCLC）. Methods In situ hybridization （ISH） with digoxin end labeled oligonucleotide probe was used to detect rnRNA expressions of cytokines in fresh pleural effusion samples and tumor tissue samples of 23 NSCLC patients. Five tuberculous pleurisy patients served as controls. Results The mRNA expression of IL-4, IL-10, TGF-α and TGF-β1 in tumor tissue and mononuclear cells from pleural effusion of NSCLC patients were significantly higher than those of IL-2, IL-12, IL-18 and INF-γ. In contrast, the mRNA expression of IL-4, IL-10, TGF-α and TGF -β1 in tuberculous pleural effusion samples was decreased. There was no significant difference in mRNA expression among different samples of tuberculous pleurisy patients. Conclusion The mRNA expressions of type Ⅱ cytokines and immunosuppressive cytokines predominated in the pleural effusion and tumor tissue of NSCLC patients, suggesting an immunosuppressive microenvironment around the tumor. The results contribute to a better under- standing of the mechanisms of tumor escape and provide an important experimental basis for working out the scheme for an effective immunomodulatory treatment of NSCLC patients.