肿瘤免疫调控机制一直是重点研究内容。业已表明，PAQR3能够感应并整合营养和氧气浓度等信号，在能量代谢和细胞稳态维持等生物学过程中具有重要的功能。最近我们通过TCGA数据库分析发现PAQR3与PD-L1 mRNA表达正相关；胃癌组织中PAQR3与PD-L1蛋白水平显著正相关，与CD8和GZMB表达负相关，是胃癌进展的危险因素；在胃癌细胞中过表达PAQR3能显著促进IFNγ诱导的PD-L1表达水平。据此我们提出肿瘤微环境感应器PAQR3促进胃癌免疫逃逸这一假说。本项目拟利用PAQR3基因敲除和过表达的胃癌细胞系，从细胞、组织及动物三个层面去阐明PAQR3是胃癌细胞免疫逃逸的重要调节因子；并采用RNAseq和磷酸化质谱筛选PAQR3调控PD-L1表达的关键蛋白或转录因子，以探索PAQR3促进胃癌免疫逃逸的潜在作用机制，为提高PD-1/PD-L1阻滞在胃癌患者中的临床反应率和疗效提供新的思路。

The mechanism of tumor immune regulation always catches the attention of many researchers. Previous studies have shown that PAQR3 can sense and integrate signals such as nutrition and oxygen concentration and play an important role in biological processes such as energy metabolism and cell homeostasis. Recently, we found a positive correlation between PAQR3 and PD-L1 mRNA expression by TCGA database analysis. PAQR3 was positively correlated with PD-L1 protein level and negatively correlated with CD8 and GZMB expression in gastric cancer tissues, which is a risk factor for the progression of gastric cancer. PAQR3 overexpression in gastric cancer cells could significantly promote PD-L1 expression induced by IFNγ. These observations led us to propose a hypothesis that tumor microenvironmental sensor PAQR3 promotes immune escape of gastric cancer. In this project, PAQR3 gene knockout and over-expression of gastric cancer cell line were used to elucidate that PAQR3 is an important regulator of immune escape of gastric cancer cells from three levels: cell, tissue and animal. RNAseq and phosphorylated mass spectrometry were used to screen the key proteins or transcription factors regulating PDL1 expression by PAQR3 in order to explore the potential mechanism of PAQR3 in promoting immune escape of gastric cancer. In order to improve the clinical response rate and efficacy of PD-1/PD-L1 block in patients with gastric cancer.