肿瘤浸润淋巴细胞（TILs）具有抑制肿瘤和促进肿瘤生长的双重效应。目前认为TILs促进肿瘤发展与肿瘤分泌特定的细胞因子有关。然而，目前肿瘤-TILs信号的调控机制还不完全清楚。我们的前期研究发现miR-128的异常低表达与CD4+FoxP3+的T细胞亚群增多相关，通过生物信息学分析TCGA数据库发现细胞因子IL16、SEMA4C和STC基因在miR-128低表达的胃癌组织中高表达，机制上我们证实miR-128可直接结合IL16基因3’UTR区域抑制其表达，而IL16可促进Treg表型的T细胞比例增加。在本项研究中，我们将利用包括细胞学、分子生物学、临床队列、人源化免疫小鼠模型方法研究miR-128通过调控肿瘤细胞因子表达影响TILs亚群变化的分子机制，研究发现将为胃癌免疫治疗提供新的理论依据。

Tumor infiltrating lymphocyte (TILs) is one of the most crucial components of the tumor infiltrating immune-cell in tumor microenvironment. Previous studies showed that TILs can exert both tumor suppressive and promoting effects, activated CTLs correlate with better survival in some cancers , Treg cells promote tumor immune escape through suppression of anti-tumor immune responses. The mechanism through which TILs may enhance tumor progression is the production of cytokines that by tumor cells can affect TILs subgroups. However, the regulatory mechanisms of Tumor-TILs signaling are only partially known. In our preliminary studies, we found that aberrantly expressed miR-128 results in increased proportion of a T cell subpopulation that is CD4+FoxP3+. We bioinformatically identified three cytokine genes, IL16, SEMA4C and STC1,are downregulated in low miR-128 expressed GC in TCGA dataset. Mechanismly, miR-128 negtively regulated IL16 expression by directly bind to two motifs located in the 3’UTR region of IL16, and IL-16 stimulation facilitated de novo induction of Foxp3+ Treg cells. In this study, we will utilize several approaches including cellular, molecular, biology clinical cohont, and immune- humanized NSG mouse model to investigate the mechanism by which miR-128 regutlates TILs subgroup through regulating cytokines expressed in GC cells. These findings will provide a new theoretical basis for GC immunotherapy