IL-17细胞因子及Th17抗原特异性淋巴细胞抗食管癌作用及机制研究

我们前期的研究发现，在食管癌的肿瘤组织中可检测到IL-17+ TIL的存在。与临床病理参数的相关性分析显示，IL-17+ TIL的数量与食管癌的T分期呈显著负相关。预后分析显示，IL-17+ TIL高数量的食管癌患者预后好，此结果初步表明了食管癌中的IL-17+ TIL具有抗肿瘤免疫作用。我们进一步的检测发现，食管癌肿瘤组织中IL-17+ TIL的数量与CD8+ CTL的数量以及CD57+ NK的数量均成正比，因此，IL-17+ TIL在食管癌中很可能是通过活化CTL以及NK细胞来发挥抗肿瘤作用。在本项目中，我们拟继续研究IL-17对于T细胞、NK细胞、中性粒细胞以及DC细胞的抗肿瘤免疫功能影响，并通过小鼠实验研究IL-17及抗原特异性Th17淋巴细胞对抑制小鼠肿瘤生长的作用，从而阐明IL-17的抗食管癌作用及机制，提供一种新的，有效的食管癌免疫治疗方法奠定基础。

In the previous study, we found that tumor infiltrating IL-17 producing cells were detected in esophageal squamous cell carcinoma tissues. clinicopathological characteristics association analysis showed that the density of IL-17 producing cells correlated negatively with T stage (depth of primary tumor invasion). Survival analysis showed that the higher densities of tumor infiltrating IL-17+ lymphocytes were associated with better overall survival of esophageal carcinoma patients. These results indicated that IL-17+ TIL play anti-tumor immunity role in esophageal carcinoma. Furthermore, we found that there were positive correlations between levels of IL-17 producing cells and the densities of CD8+cells, as well as CD57+cells in esophageal tumor tissues. Thus, IL-17+ TIL might play anti-tumor immunity role through activating CTL and NK cells in esophageal carcinoma. In the present study, we plan to further investigate the IL-17 effects to the anti-tumor immunity of T cells, NK cells, neutrophile and dendritic cells in vitro. And using mouse model, the tumor growth inhibiton effects in vivo of IL-17 and antigen specific Th17 lymphocytes were also study. This study can help to better understand the anti-esophageal carcinoma mechanism of IL-17. This study also will establish good fundation for developing novel, effective immunotherapy methods to esophageal carcinoma in the future.