Together,Elevated Alternatively Activated Macrophages,Myeloid-Derived Suppressor Cells and Th2 Cells Polarization Foster an Immunosuppressive Environment in Esophageal Cancer Patients

【作者】 高晶晶； 吴玉敏； 焦志军； 苏兆亮； 夏圣； 邵启祥； 王胜军； 许化溪；

【机构】 江苏大学免疫学与临床免疫检验系；

【摘要】 Background:During carcinogenesis,myeloid derived suppressor cells(MDSCs)and M2 macrophages,as major host components contributing to the suppressive environment of tumor immunity.Previously we showed that there was a predominant Th2 phenotype in cancer patients,but it is not known whether the polarization of Th2 cells also relate to this immunosuppression in esophageal cancer.Methods:MDSCs,M2 macrophages and Th2 cells associated cytokines mRNA and protein expression levels were investigated in esophageal cancer patient samples using quantitative real-time PCR and ELISA analyses.In addition,immunohistological studies were carried out to determine CD68 and CD163,the M2 macrophage biomarkers,in esophageal cancer tissues and paired adjacent tissues.The frequency of the MDSCs in peripheral blood was detected by flow cytometer analysis.Results:The level of the MDSCs in PBMC and Argl in plasma were significantly elevated in patients,especially in advanced cancer,and a positive correlation was found between MDSCs and plasma level of Argl in ECA patients,Moreover,the increased expressions of CD68 and CD 163 were found in cancer tissues.We also demonstrated that ECA patients exhibited remarkable increases in the mRNA levels of IL-4 and GATA3,as well as the plasma levels of IL-13 andIL-6.In contrast,plasma levels of IFN-γand mRNA levels of IFN-γ,IL-10 and IL-12 were decreased.In addition,the changes of IL-4 and IL-13 levels correlated positively with MDSC and M2 macrophages activation,but IFN-γplayed the opposite effect.Conclusions:The increased Th2 cells associated cytokines is associated with MDSCs and M2 macrophages polarization,it contribute to immunosuppressive environment in esophageal cancer.更多还原

【Abstract】 Background:During carcinogenesis,myeloid derived suppressor cells(MDSCs) and M2 macrophages,as major host components contributing to the suppressive environment of tumor immunity.Previously we showed that there was a predominant Th2 phenotype in cancer patients,but it is not known whether the polarization of Th2 cells also relate to this immunosuppression in esophageal cancer.Methods:MDSCs,M2 macrophages and Th2 cells associated cytokines mRNA and protein expression levels were investigated in esophageal cancer patient samples using quantitative real-time PCR and ELISA analyses.In addition,immunohistological studies were carried out to determine CD68 and CD163,the M2 macrophage biomarkers,in esophageal cancer tissues and paired adjacent tissues.The frequency of the MDSCs in peripheral blood was detected by flow cytometer analysis.Results:The level of the MDSCs in PBMC and Arg1 in plasma were significantly elevated in patients,especially in advanced cancer,and a positive correlation was found between MDSCs and plasma level of Argl in ECA patients,Moreover,the increased expressions of CD68 and CD163 were found in cancer tissues.We also demonstrated that ECA patients exhibited remarkable increases in the mRNA levels of IL-4 and GATA3,as well as the plasma levels of IL-13 and IL-6.In contrast,plasma levels of IFN-γ and mRNA levels of IFN-γ,IL-10 and IL-12 were decreased.In addition,the changes of IL-4 and IL-13 levels correlated positively with MDSC and M2 macrophages activation,but IFN-γ played the opposite effect.Conclusions:The increased Th2 cells associated cytokines is associated with MDSCs and M2 macrophages polarization,it contribute to immunosuppressive environment in esophageal cancer.更多还原