原位杂交检测胃癌组织中几种细胞因子的mRNA变化

目的　了解早期胃癌向晚期胃癌进展中 ,局部免疫微环境的变化。方法　用地高辛标记的寡核苷酸探针原位杂交技术 ,检测 1 3例早期胃癌 ,2 0例晚期胃癌组织中与调节免疫反应密切相关的IFN γ、IL 2、IL 1 0、GM CSF、TGF β五种细胞因子mRNA表达的情况。 结果　胃癌进展过程中 ,IFN γ/IL 1 0比值明显下降 ,Th2型反应随肿瘤进展而加重 ;随着疾病的进展 ,肿瘤间质及实质中IFN γ、IL 2阳性细胞减少 ,几乎难以找到 ;Th2型因子IL 1 0和TGF βmRNA在瘤实质的表达明显增强 (P <0 0 5 ) ,且IL 1 0与TGF β表达的增多主要是由于肿瘤细胞大量表达所致。结论　胃癌进展过程中 ,局部Th2型反应逐步增强 ,免疫抑制逐渐加深。肿瘤局部微环境的这种变化为肿瘤逃逸宿主免疫监视提供了有利条件。这些发现为设计肿瘤免疫治疗方案提供了依据。

Dynamic change of the local immune environment of human gastric carci noma during the progress of this disease

Objective To understand the dynamic changes of local immune microenvironment during the progress of gastric carcinoma from early to advanced stage. Methods The mRNA expression of cytokines including IL-2, IFN-γ, IL-10, TGF-β and GM-CSF in 13 specimens of early stage and 20 cases of advanced gastric carcinoma, were investigated by the Digoxenin-labeled Oligonucleotide-probes In Situ Hybridization(ISH).Results With the progress of gastric carcinoma, the expression of IFN-γ and IL-2 in lymphocytes were decreased evidently; while the expression of TGF-β and IL-10 mRNA in tumor cells and also in TILs increased significantly( P <0.05); The elevated expression of IL-10 and TGF-β was mainly because of the high expression of tumor cells. Conclusion At the tumor site, the immune response was mainly Th2-type and it deteriorate with the tumor progression. The degree of suppression deepened continually. In all, during the gastric carcinoma grow larger, local Th2-type immune response deteriorate which might be resulted from the expression of TGF-β and IL-10 by tumor cells. This might be helpful for the design of tumor immunotherapy.