化疗或化疗联合免疫治疗是目前胃癌尤其是晚期患者主要的治疗方案，但临床化疗的有效率并不理想，主要是由于胃癌细胞存在多药耐药性(MDR)。近期研究报道癌细胞PD-L1高表达可促进化疗耐药及缩短患者生存时间，我们也发现血浆PD-L1水平明显增高的胃癌患者化疗效果较差，但其确切机制不明。我们前期研究发现胃癌间质干细胞（GCMSCs）调节c-Myc上调胃癌细胞PD-L1表达，且能促进胃癌细胞对化疗药物抵抗，其分子作用机制有待本课题进一步研究。本课题将采用细胞及分子生物学技术阐明GCMSCs促进胃癌细胞PD-L1表达的关键分子及导致化疗耐药的作用及机制。基于小鼠胃癌模型及胃癌化疗患者评估，确立胃癌化疗联合免疫治疗的新靶点，为胃癌患者筛选、预后判断及疗效提高等提供帮助，并建立提高胃癌化疗有效性的新策略。

Chemotherapy or chemotherapy combined with immunotherapy is the main treatment for clinical gastric cancer, especially for advanced patients, but the efficacy of clinical chemotherapy is not ideal, mainly due to the existence of multidrug resistance (MDR) in gastric cancer cells. Recent studies have reported that the high expression of PD-L1 in cancer cells can promote drug resistance and shorten the survival time of patients. We also found that the effect of chemotherapy in gastric cancer patients with significantly increased plasma PD-L1 level is poor, but the exact mechanism is unclear. We have previously demonstrated that GCMSCs are capable of up-regulating the expression of PD-L1via regulating c-Myc in gastric cancer cells coincides with promoting gastric cancer cells against chemotherapeutic drugs, but the molecular mechanism needs further study in this project. In this project, we will seek the key factors derived from GCMSCs that regulate the expression PD-L1 of gastric cancer cells by cellular and molecular biology approaches and the effect and mechanism of inducing chemotherapeutic resistance. Based on the mouse gastric cancer model and the evaluation of clinical gastric cancer chemotherapy patients, we will establish a new target of chemotherapy combined with immunotherapy for gastric cancer, providing help for gastric cancer patients' selection, prognosis and improving efficacy, and establishing a new strategy to improve the effectiveness of chemotherapy for gastric cancer.