树突状细胞DCs的表型和功能与糖代谢密切相关。胰腺癌组织浸润DCs呈现免疫耐受性，其功能重塑受细胞内炎性通路和糖代谢通路等调控。胱天蛋白酶募集域蛋白CARD9为主要表达于DCs和巨噬细胞中的调控多条信号通路传导的衔接蛋白，在炎症信号转导过程中发挥重要作用。前期研究发现伴随胰腺癌发生发展DCs免疫原性降低，胞内CARD9表达下调；此外，CARD9的表达影响了糖吸收、糖酵解相关基因和蛋白表达及糖代谢产物产生。CARD9是否介导DCs糖代谢和功能重塑未见报道。我们拟用胰腺癌转基因动物模型和肿瘤微环境模型，以CARD9关联的炎性通路NF-κB和糖代谢通路MAPK/P38、PI3K/Akt/FoxO1为切入点，研究CARD9调控DCs糖酵解和氧化磷酸化等糖代谢，改变DCs免疫功能，介导胰腺癌发生发展的作用及机制，以揭示胰腺癌DCs糖代谢和功能重塑的新机制和基于DCs的胰腺癌肿瘤免疫治疗新方法。

The phenotype and function of dendritic cells (DCs) are closely related to glucose metabolism. The tumor tissues infiltrated DCs of pancreatic cancer exhibit immunotolerant properties, which are regulated by intracellular inflammation pathway and glucose metabolism pathway. CARD9 (caspase-associated recruitment domain 9) is an important adapter protein that regulates multiple signaling pathways in DCs and macrophages, and plays an important role in inflammatory signal transduction. Our previous studies found that the immunogenicity of bone marrow-derived DCs decreased in the progression of pancreatic cancer, which was accompanied with downregulated CARD9 expression. CARD9 altered glucose uptake, expression of glycolysis-related genes and proteins, acidic metabolites of DCs. Whether CARD9 modulates the glucose metabolism and function remodeling of DCs has not been reported. We intend to investigate how CARD9 regulates the glycolysis, oxidative phospholation and function remodeling of DCs in the transgenic animal models and tumor microenvironment of pancreatic cancer, by modulating the inflammation-related NF-κB pathway and metabolism-related MAPK/P38, PI3K/Akt/FoxO1 pathways in DCs. Our study will elucidate the new molecular mechanism underlying glucose metabolism and function remodeling of DCs in pancreatic cancer, and new approach for immunotherapy based on DCs.