喉鳞癌中趋化因子受体介导CD4+CD25+调节性T细胞增殖的作用机制研究

项目名称： 喉鳞癌中趋化因子受体介导CD4+CD25+调节性T细胞增殖的作用机制研究

项目编号： No.30801283

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 陶磊

作者单位： 复旦大学

项目金额： 21万元

中文摘要： 喉鳞癌是耳鼻咽喉头颈外科常见的恶性肿瘤之一，近年来发病率不断上升。通过喉癌组织和外周血的检测，发现喉癌患者外周血中CD4+CD25+Foxp3+Treg细胞属于诱导性调节性T细胞，其表面可表达CCR6和CCR7，其可通过产生IL-10和TGF-beta抑制喉癌患者的细胞免疫功能，其外周血所占百分比较正常人显著增加，并与临床分期相关；喉鳞癌组织中CCR6、CCR7呈阳性表达，且与肿瘤TNM、临床分期、淋巴结转移相关；喉癌组织高表达CCL20，对Treg和肿瘤细胞具有潜在的趋化能力；喉癌患者CD4+CD25+CCR6+Treg细胞Foxp3的表达，以及喉鳞癌组织Foxp3 mRNA的表达皆明显高于对照组，且与临床分期、淋巴结转移相关。研究还发现，喉癌组织只表达了分子量为54 kDa的磷酸化JNK（JNK2），而46 kDa的磷酸化JNK（JNK1）不表达，HEp-2喉癌细胞系则不表达磷酸化的JNK，提示JNK信号通路可能具有抑制肿瘤生长的作用。

中文关键词： 喉鳞癌；CD4+CD25+Foxp3+调节性T细胞；趋化因子；受体;淋巴结转移

英文摘要： Laryngeal squamous cell carcinoma(LSCC) is one of the most common malignancy in Otolaryngology-Head and Neck Surgery, whose incidence has increased in recent years.By using fresh laryngeal tissues and peripheral blood, we found that 1) CD4+CD25+Foxp3+ Treg, expressing chemokine receptor CCR6 and CCR7, can down-regulate the immunity of LSCC patients by expressing IL-10 and TGF-beta, whose percentage in LSCC patients was significantly higher than that of normal subjects. 2) both CCR6 and CCR7 expressed in LSCC tissues whose expression levels were related to TNM stage, clinical stage and lymph node metastasis. 3) LSCC tissue highly expressed CCL20, which may promote the chemotaxis of Treg potentially; 4) the expression level of Foxp3 in CD4+CD25+CCR6+ Treg cells and fresh tissue were significantly higher in LSCC paients, which alse related with the clinical stage, lymph node metastasis. 5) we also detected phosphorylated JNK (JNK2, MW=54 kDa), not JNK1 (MW=46 kDa), in fresh LSCC tissue, but the phosphorylated JNK was not detected in HEp-2 cell line, indicating JNK signaling may inhibit tumor growth.

英文关键词： Laryngeal squamous cell carcinoma；CD4+CD25+Foxp3+ regulatory T cells；Chemokine Receptor；Ligand；Lymphatic metastasis