以免疫检查点为靶标的免疫调节治疗在多种难治性肿瘤的临床试验中获得突破，然而在胰腺癌的研究中却未能改善预后。深入分析，我们认为不同微环境中肿瘤免疫重塑的差异是影响治疗效果的关键。乏氧微环境在胰腺癌的进展及放化疗抵抗中发挥重要作用，然而乏氧微环境对胰腺癌局部免疫重塑的影响及机制尚未阐明。文献报道免疫检查点PD-L1在胰腺癌中表达增加。我们研究发现高表达PD-L1的胰腺癌患者预后差，乏氧状态下胰腺癌细胞PD-L1表达与Foxp3表达以及肿瘤局部Treg细胞浸润呈显著正相关。转录因子Foxp3参与乏氧状态下胰腺癌免疫逃逸，本研究拟阐明乏氧环境中胰腺癌细胞Foxp3对PD-L1表达的调控机制；探讨乏氧微环境下胰腺癌细胞PD-L1与Treg细胞间的交互网络在胰腺癌免疫逃逸中的作用及内在机制；进而针对胰腺癌乏氧微环境和免疫重塑特征，探索新的联合免疫治疗方案，为胰腺癌治疗的基础研究与临床转化提供理论依据。

Checkpoint-targeted immune therapy has breaked through in multiple clinical trials of refractory tumors, but it didn't improve prognosis in pancreatic cancer. We believed a complex nature of tumor immunity rebuilding served as the key of therapy efficacy. Hypoxia played an important part in the progression and the radio-chemotherapy resistance in pancreatic cancer, while its role in local immunity-rebuilding still remain to be elucidated. Previous study showed that checkpoint PD-L1 expression increased in pancreatic cancer. In our experiments, we discovered that patients with high expression of PD-L1 associated with a poor prognosis, and that PD-L1 expression under hypoxia positively correlated with FOXP3 expression and Treg infiltration. Transcription factor FOXP3 participates in the immunology escape in pancreatic cancer under hypoxia. This study aims to clarify the regulation mechanism of PD-L1 by FOXP3 under hypoxia condition, and further investigates the function and mechanism of PD-L1-Treg network exerted on the immune escape in pancreatic cancer. We explore new combination immune therapy based on the hypoxia and immunology rebuilding microenvironment of pancreatic cancer, thus providing theory evidence for the basic research and clinical translation for future treatment of pancreatic cancer.