胃癌是威胁我国人民健康的主要恶性肿瘤，中性粒细胞是胃癌微环境浸润最多的免疫细胞，明确胃癌相关中性粒细胞在胃癌微环境中的免疫病理效应对揭示胃癌进展的免疫学机制具有重要科学意义。前期发现，肿瘤来源的炎症因子GM-CSF和IFN-γ能够显著诱导胃癌相关中性粒细胞表达凋亡相关分子Fas-L；胃癌相关中性粒细胞则可通过Fas-L-Fas通路介导效应T细胞凋亡。因此，本项目拟以胃癌相关中性粒细胞为研究对象，采用分子生物学技术和荷瘤动物模型，（1）明确Fas-L在胃癌相关中性粒细胞表达的临床意义；（2）探索Fas-L+胃癌相关中性粒细胞介导效应T细胞凋亡的相关通路及分子级联机制；（3）揭示胃癌微环境上调中性粒细胞表面Fas-L表达的调控机制；（4）验证Fas-L+胃癌相关中性粒细胞促进胃癌进展的效应机制。相关研究是对胃癌免疫耐受机制的重要补充，并可为胃癌的免疫防治提供新的靶点及理论依据。

Gastric cancer（GC） is one of the leading causes of death in China. Neutrophil is one of the most abundant immune cells infiltrated in GC. It is of great importance to illustrate the immunopathological effects of GC-associated neutrophils in tumor progression. Previously, we found that GC-derived GM-CSF and IFN-γ up-regulated Fas-L expression on GC-associated neutrophils and Fas-L+ GC-associated neutrophils mediated effector T cell apoptosis through Fas-L-Fas pathway. Thus, we aim at these GC-associated neutrophils, and intend to investigate (1) the clinical significance of Fas-L expression on these GC-associated neutrophils; (2) the pathways and molecular cascade mechanisms of GC-associated neutrophils in mediating effector T cell apoptosis; (3)the regulating mechanism of Fas-L expression on GC-associated neutrophils by GC-derived GM-CSF and IFN-γ; (4）the GC promotion effect of Fas-L+ GC-associated neutrophils in vivo; by related molecular biology technologies and tumor-bearing mice. This study may be an important complementation to the mechanism of GC immune tolerance and provide new therapy targets and theoretical basis for the treatment of GC.