NNMT高表达促胆囊癌M2型TAM聚集及免疫逃逸的机制研究

肿瘤免疫逃逸是影响胆囊癌患者预后和化疗有效性的重要危险因素。本课题组发现胆囊癌过表达NNMT可能导致免疫逃逸的发生，NNMT上调后促进肿瘤组织M2型TAM的聚集，并介导免疫逃逸，通过RT-PCR实验分析筛选出与NNMT相关性最大的免疫抑制分子IL6。本课题拟在前期工作基础上利用动物模型和体外共培养实验从动物水平和细胞水平进一步明确NNMT对M2型TAM功能的影响，揭示NNMT的过表达导致胆囊癌免疫逃逸的具体分子机制。最后通过利用特异性的NNMT抑制剂来改善肿瘤免疫微环境，从而试图达到提供治疗效果的目的。本项目的研究不仅有助于阐明NNMT抑制胆囊癌免疫逃逸的分子机制，而且能为胆囊癌治疗提供新思路和新靶点。

Tumor immune escape is an important risk factor affecting the prognosis and the effectiveness of chemotherapy in patients with gallbladder cancer.Our team found that overexpression of NNMT in gallbladder cancer may lead to immune escape,the upregulation of NNMT may promote the M2 like TAM accumulation which suppress T-cell function and trigger immune escape .Through RT-PCR analysis, we screened out the immuno-suppressive molecule IL6 which is most related to NNMT. Thus,On the basis of previous work we plan to use animal model and in vitro co culture experiment to study the immune escape from animal level and cell level ,to further clarify the effect of nnmt on the function of M2 like TAM, and reveal the specific molecular mechanism of NNMT overexpression leading to immune escape in gallbladder cancer. Finally,we try to achieve the purpose of providing therapeutic effect by using specific NNMT inhibitors to improve the tumor immune microenvironment.This project not only helps to clarify the molecular mechanism of NNMT inhibiting immune escape in gallbladder cancer, but also provides new ideas and new targets for the treatment of gallbladder cancer.