非小细胞性肺癌局部免疫微环境中细胞因子mRNA表达的分析

目的:以非小细胞肺癌(non-small cell lung cancer,NSCLC)为对象,探讨肿瘤局部微环境中免疫反应的特点及其对抗肿瘤免疫的影响。方法:以5例结核性胸膜炎患者作为对照,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例非小细胞性肺癌(NSCLC)患者的新鲜胸腔积液和/或手术切除标本中的淋巴细胞和肿瘤细胞中,IL-2、INF-γ、IL-12(p40)、IL-18、IL-4、IL-10、TGF-β1、IL-1、IL-3、IL-8、GM-CSF、TNF-α及TGF-αmRNA的表达。结果:NSCLC患者胸腔积液的单个核细胞及肿瘤组织中,IL-4、IL-10、TGF-α和TGF-β1mRNA的表达水平,明显高于IL-2、IL-12、IL-18和INF-γmRNA的表达;而结核性胸腔积液的单个核细胞中上述细胞因子mRNA的水平均降低,并且各细胞因子mRNA的表达水平之间没有明显的差异。结论:NSCLC患者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。

The in situ analysis of cytokine mRNA expression in immunological microenvironment about non-small cell lung cancer

AIM: Using Non-small cell lung cancer (NSCLC) as subject, to explore the characteristics of immune response in immunological microenvironment at the tumor site and its effect on anti-tumor immunity. METHODS: Using in situ hybridization (ISH), the expressions of IL-2, INF-gamma, IL-12 (p40), IL-18, IL-4, IL-10, TGF-beta1, IL-1, IL-3, IL-8, GM-CSF, TNF-alpha and TGF-alpha mRNAs in lymphocytes and tumor cells from five fresh pleural effusion samples and 18 tumor tissue samples of NSCLC patients were detected by in situ hybridization with digoxin end-labeled oligonucleotide probe, using 5 tuberculous pleurisy patients as control. RESULTS: In pleural effusion and tumor tissue of NSCLC patients, the expression levels of IL-4, IL-10, TGF-alpha, and TGF-beta1 mRNAs were significantly higher than those of IL-2, IL-12, IL-18 and INF-gamma mRNAs. In contrast, the analysis of tuberculous pleural effusion samples revealed lower levels of above-mentioned cytokine mRNA. There was no significant difference among expression levels of these cytokine mRNAs. CONCLUSION: The expressions of type II cytokine mRNAs and immunosuppressive cytokine mRNAs in pleural effusion and tumor tissue of NSCLC patients occupied a dominant position, suggesting that the immunological microenvironment about tumor be in an immunosuppressive state. The present study has contributed to a better understanding the mechanisms of tumor escape and provides important experimental basis for working out the scheme for an effective immunomodulatory treatment of NSCLC patients.