Between Bone Marrow Mesenchymal Stem Cells To Pancreatic Ductal Adenocarcinoma. Study Of Effects Of Immunosuppression

Background and Purpose:Emerging information demonstrates human mesenchymal stem cells in peripheral blood may be related to tumor growth, but their actual involvements have not been illustrated in pancreatic ductal adenocarcinoma (PDAC) The aim of this study was to investigate change of MSCs and regulatory T cells (Treg cells) in peripheral blood of pancreatic cancer patient. Meanwhile, we want to assess effect of MSCs on Treg cells and immune suppression factors in pancreatic cancer patient’s immune microenvironment and their pathologic character.Methods:We collected peripheral blood sample of30pancreatic ductal adenocarcinoma patients who visited ZhongShan hospital from2011-6to2012-3. Human MSCs and Treg cells were isolated from peripheral blood by density gradient centrifugation, and MSCs phenotype and percentage by immunoflurosence flow cytometry to identify. Enzyme-linked immunosorbent assay (ELISA) was apply to measure expression of immune suppression factors such as Vascular Endothelial Growth Factor (VEGF), Fibroblast Growth Factor (FGF) and Interleukin-6(IL-6) in serum. We collected paraffin-embedded pathological slices of40pancreatic ductal adenocarcinoma patients from2009-6to2010-12which stored in pathological Department of Zhongshan HospitalFudan University. Immunochemistry staining was dectected Tumor associated fibroblasts, CAFs (FAP positive cells) and dendritic cells, DC (CD1a positive cells) in pancretic cancer.Results:The results indicated that the number of MSCs and Treg cells was significant increased in the peripheral blood of pancreatic ductal adenocarcinoma patient compared with control group (p<0.05). ELISA results demonstrated immune suppression factors VEGF, FGF and IL-6expression in serum were higher than control group. Meanwhile, we found a majory of CAF cells were detected in PDAC compared with control group and their expression associated with tumor size.However, the number of DC cells obviously reduced in PDAC group compared with control group and associated with tumor size and lymph node metastasis.Statistics analyze results display there is a positive correlation between Treg and different growth factor in pancreatic cancer. Conclusion:Increased of mesenchymal stem cells and Treg cells in the peripheral blood of pancreatic ductal adenocarcinoma patient may involve into tumors formation and growth. Treg cells may effect immune microenvironment by regulating immune suppression factors expression. Correlation analysis show increased of Treg cells is related to expression of immune suppression factors. Treg cells may induce immune microenvironment’immune suppression state by secreting immune suppression factors.In addition, clinical pathological index display tumor associated fibroblasts (CAF) is related to tumor size, dendritic cells (DC) expression is related to tumor size and lymphatic metastasis.