癌细胞通过产生肿瘤源性因子(TDFs)诱导免疫细胞功能转化，促肿瘤免疫逃逸。前期发现：胰腺炎症分子Reg3除通过经典促增殖作用参与胰腺炎症恶性转化外，尚抑制动物树突状细胞(DCs)功能，且在胰腺癌(PaC)细胞中有自身诱导现象。据此推测：PaC细胞持续分泌的Reg3，以TDF身份训导位于免疫调节上游的DCs，营造免疫抑制微环境以利肿瘤逃逸进展。本研究拟以shRNA、过表达质粒对PaC细胞的Reg3进行干预，体外Transwell模型中PaC细胞/人外周血来源DCs共培养，明确肿瘤源性Reg3在PaC微环境影响DCs中的关键作用；免疫重建SCID小鼠PaC移植瘤模型DCs过继转移，了解肿瘤源性Reg3训导后的DCs对PaC在体进展的影响；以JAK/STAT3,NF-κB及EGFR等为切入点，分析肿瘤源性Reg3驯导DCs的可能机制。以期全面揭示Reg3在胰腺炎症恶性转化中关键效应和调控规律。

Cancer cells can release a variety of tumour-derived factors (TDFs) to induce the functional shift of immune cells, which could then facilitate tumor escape through evasion of immune surveillance. Our previous researches found that Regenerating islet-derived protein 3 (Reg3), an inflammatory molecule highly expressed in pancreatic tissue, contributed to inflammation-related pancreatic cancer (PaC) development via its proliferation-promoting effect; mice treated with a lentivirus system encoding for Reg3 displayed suppressed dendritic cell(DC) function; and overexpression of endogenous Reg3 was found in PaC cells treated with exogenous Reg3,indicating its self-induction. These results suggested that: Reg3 continuously released by PaC cells could act as a TDF to “educate” DCs, the most important antigen presenting cells, contribute to immunosuppressive tumor microenvironment and facilitate PaC escape and progression. In this research, short-hairpin RNA (shRNA) / lentivirus plasmids will be used to silence/ over-express Reg3 in different PaC cells, then human peripheral blood-derived DCs will be co-cultured with PaC cells in a Transwell co-culture system, to confirm the role of tumour-derived Reg3 in the regulation of PaC microenvironment to the differentiation, survival and function of DCs; the effects of tumour-derived Reg3-educated DCs on PaC progression will be determined by intraperitoneal transfer in PaC-implanted SCID mice reconstituted with T cells; the expression of JAK/STAT3, NF-κB and possible Reg3 receptor EGFR in tumour-derived Reg3-educated DCs will be studied to investigate the mechanism. This study focuses on the new immune modulating function of Reg3 as a TDF responsible for immune escape of PaC, to further reveal the multifunctional role of Reg3 in the inflammation-linked pancreatic carcinogenesis.