关键趋化因子对食管鳞癌预后和治疗的影响研究

项目名称： 关键趋化因子对食管鳞癌预后和治疗的影响研究

项目编号： No.81502689

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李峰

作者单位： 郑州大学

项目金额： 18万元

中文摘要： 食管鳞癌在我国高发且预后较差，患者5年生存率低于20%。肿瘤复发是造成死亡的重要原因。准确判断预后，及时给予高危患者治疗将改善生存，但尚无有效预后指标。鉴于CD8+ T细胞和Treg细胞对肿瘤发展和预后的巨大影响，决定T细胞浸润的关键趋化因子可能成为有效预后指标。前期研究发现CCL4、CCL5和CCL20在肿瘤组织高表达，可能是影响T细胞归巢和患者预后的关键趋化因子。本研究中，将探索这3种趋化因子对CD8+ T细胞和Treg细胞浸润肿瘤的影响以及与预后的相关性，探讨趋化因子影响预后的免疫机制。研究趋化运动还有助于新型治疗技术开发。趋化因子通过特异受体指导细胞运动，前期研究提示特异受体表达与CIK细胞治疗效果密切相关。本研究中，我们将提高特异受体CCR5和CCR6在CIK细胞中的表达，并观察CIK细胞靶向运动能力和肿瘤清除之间的关系，为细胞输注治疗效果改善提供数据参考。

中文关键词： 食管鳞癌；趋化因子；趋化因子受体；CIK细胞；预后

英文摘要： The incidence rate of esophageal carcinoma is high in China. Among esophageal carcinoma patients, esophageal squamous cell carcinoma (ESCC) accounts for 90% of cases. The prognosis of ESCC patients is poor. Due to relapse happens in 70%-80% patients after treatment, the 5-year survival rate is below 20%. However, proper implementation of salvage strategies would prolong ESCC patients survival. Thus, it is necessary to identify available prognostic factors for predicting response to treatment and clinical outcomes of ESCC patients. Tumor immune microenvironment factors are tightly correlated with prognosis. Among them, chemokines deciding the infiltrations of T lymphocyte subgroups into tumors are potential candidates to predict the clinical outcomes of ESCC patients. In ESCC, the clinical significances of chemokines and related T lymphocyte movement have been neglected. In this project, we will explore how chemokines CCL4, CCL5 and CCL20 are involved in the recruitment of T lymphocyte subsets into ESCC. Furthermore, follow-up study will be performed to verify the possibility that chemokines predict ESCC patients prognosis. In addition, we will check whether the expression of specific chemokine receptor improve therapeutic efficacy of CIK cells. Employing lentiviral expression system, CCR5 (receptor for CCL4 and CCL5) and CCR6 (receptor for CCL20) are expressed on CIK cells. Then the tumor-targeted migration will be checked in vivo. Our data would help to develop new modalities for ESCC therapy.

英文关键词： esophageal squamous cell carcinoma;chemokine;chemokine receptor;CIK cell;prognosis