Research On The Role Of CCR9 In Plasmacytoid Dendritic Cells Mediated Immunosuppressive Microenvironment Of Human Gastric Cancer

Objective:Plasmacytoid dendritic cells(PDCs)play a crucial role in the immunosuppressive microenvironment of tumor.At present,it has been found that chemokine receptor 9 is an important molecule that directs PDCs homing to the digestive tract.CCR9+PDCs are involved in the formation of digestive tract immune tolerance.The aim of this study was to explore the role of CCR9 in PDC-mediated immunosuppression microenvironment of human gastric cancer.Methods:We detected the populations of Tregs and PDCs in carcinoma tissue and normal gastric mucosa from 140 GC patients by immunohistochemistry.Immunofluorescence was used to detect the distribution of CCR9+PDC between carcinoma tissue and normal gastric mucosa.In addition,Western Blot was applied to evaluate the expression of CCL-25 in gastric mucosa.Peripheral blood and draining lymph nodes were analyzed for PDCs,eCR9+PDCs,eCR9-PDCs,Tregs,ICOS+Tregs and ICOS-Tregs by flow cytometry.Plasma concentration of the cytokines IL-2,IL-6,IL-10 and et al were measured by enzyme-linked immunosorbent assay(ELISA)as well.Results:1.Numbers of total Tregs,PDCs and CCR9+PDCs were higher in carcinoma tissue than that in normal gastric mucosa.2.In tissue,the expression of CCL-25 was increased in gastric tissue.3.The numbers of PDCs?CCR9-PDCs?Tregs?ICOS+Tregs?ICOS-Tregs in peripheral blood were significantly increased in GC patients compared with healthy people.4.More PDCs?CCR9+PDCs?Tregs?ICOS+Tregs were found in metastatic lymph nodes in comparison with non-metastatic lymph nodes.5.The concentration of IL-2 was lower,the level of IL-6 and IL-10 were higher in GC patients compared with healthy donors.6.Under different stages or lymph nodes metastasis,there were no differences between PDCs or Tregs.Conclusions:Number of the regulatory T cells were increased in gastric tissue,which prompted the formation of immunosuppressive microenvironment;CCR9 might play an important role in mediating plasmacytoid dendritic cells homing to gastric cancer and exerting the negative control of the immune system.