乳腺癌髓系来源抑制细胞中IDO表达与调节性T细胞相关性及其临床意义的研究

Clinical Significance of the Correlation between IDO Expression in Myeloid-derived Suppressor Cells and Regulatory T Cells in Breast Cancer

目的:研究不同期别乳腺癌组织中CD33^+髓系来源抑制细胞(MDSCs)和Foxp3^+调节性T细胞(Tregs)的分布情况,探讨MDSCs中吲哚胺2,3-双加氧酶(IDO)表达与Tregs分布关系及其临床意义。方法:收集天津医科大学附属肿瘤医院2005年1月至2007年1月手术患者的乳腺癌石蜡切片50例,采用免疫组织化学单染方法对肿瘤局部CD33^+MDSCs和Foxp3^+Tregs分布和比例进行检测;采用免疫组织化学双染方法检测肿瘤原位浸润MDSCs中IDO的表达情况;分析MDSCs中IDO表达与Tregs分布、比例及其他临床病理资料之间的相关性。结果:Foxp3^+Tregs和CD33^+MDSCs细胞在乳腺癌组织中呈散在性分布。MDSCs中IDO表达水平与腋窝淋巴结转移密切相关(P<0.05)。Foxp3^+Tregs高表达组中MDSCs中IDO表达水平显著高于Foxp3^+Tregs低表达或不表达组(P<0.05)。结论:MDSCs中IDO过表达可能有利于Tregs的募集和乳腺癌的转移。

Objective： Myeloid-derived suppressor cells （ MDSCs ） are the important inhibitory immune cells in the tumor microenvironment that are directly involved in tumor immune escape and metastasis. This study aims to determine the distribution of CD33^＋MDSCs and regulatory T cells （ Foxp3^＋Tregs ） in breast cancer tissues, to detect IDO protein expression in CD33^＋MDSCs, and to analyze the correlation between IDO expression in MDSCs and distribution of Foxp3＋Tregs in breast carcinoma tissues, as well as their clinical sig- nificance. Methods： Paraffin-embedded samples were collected from 50 breast cancer patients who underwent surgery in Tianjin Medical University Cancer Institute and Hospital between January 2005 and January 2007. The distribution of CD33^＋ MDSCs and Foxp3^＋ Tregs in the breast cancer tissues of different stages was evaluated using immunohistochemical staining （ IHC ）. The protein expression and cell localization of CD33 and Foxp3 were detected using the single-dye IHC method, whereas the IDO expression in the CD33^＋MDSCs was detected using the double-dye IHC method. The correlation between IDO＋MDSCs and Foxp3＋Tregs in breast carcinoma samples and the relationship among the clinicopathologic features was analyzed. Results： The Foxp3^＋Tregs and CD33＋MDSCs were sporadically distributed in the breast cancer tissues. The IDO expression levels in the MDSCs were closely correlated with axillary lymph node metastasis （ P 〈 0.05 ）. More Foxp3＋Tregs were observed in the cancer tissues with higher IDO expression levels in MDSCs compared with tissues with lower IDO expression levels （ P 〈 0.05 ）. Conclusion： IDO expression in MDSCs might benefit the recruitment of Tregs and promote the metastasis of breast cancer.