Characters Of Cytokines Expression And A Mixed-Phenotype Of Tumor-Associated Macrophages In Peritoneal Environment Of Ovarian Cancer

Objectives:Ovarian cancer represents?3%of newly diagnosed cancers in women,but also presents the most deadly female reproductive tract disease.Epithelial ovarian cancer(EOC)has a distinct predisposition to metastatic involvement of the peritoneal cavity lining.The submesothelial stroma of the peritoneum of EOC patients has an extensive infiltrate of inflammatory cells.Macrophages(MA)have emerged as a critical component of the inflammatory microenvironment in tumors.Macrophages within the tumor microenvironment—tumor-associated macrophages(TAMs)—promote cancer initiation and malignant progression.This study investigates the following:1)proportions of tumor-associated macrophage and its subpopulations in the ascite of ovarian cancer(OC)patients,2)expression of mammalian homologs of the toll-like receptors(TLRs)in different TAMs subpopulations and 3)the cytokine profiles in the peritoneal microenvironment.Methods:Proportions of TAMs and its subpopulations were identified by flow cytometry.RNA assessment of TLR was performed by real-time polymerase chain reaction.The concentrations of cytokines in ascites were detected by enzyme-linked immunosorbent assay(ELISA)kits.Results:1)CD68+TAMs in the ascite exhibited no difference between OC patients and those with benign tumor(P>0.05).However,Ml macrophage in OC ascites was significantly less than those found in benign tumor(30.5%vs.53.3%;P<0.01).M2 macrophage in OC ascites was significantly higher than those found in benign tumor(54.3%vs.10.1%;P<0.05).2)TLR level was similar in Ml and M2 macrophages(P>0.05).3)The cytokines expressed in peritoneal environment revealed IL-6 high,IL-10 high,IFN-y low in ascite of OC,While IFN-y high,IL-6 low,IL-10 low in benign tumor.However,no significatively differences were observed in expression of LPS,HMGB1,IL-4 and IL-13.Conclusions:A mixed-phenotype of tumor-associated macrophages was found in the peritoneal environment.M2 macrophages were dominant in the ascite of OC,whereas M1 macrophages were predominant in the benign tumor.TLRs were not the key factors that affected the polarization of macrophages.While cytokines of peritoneal microenvironment may effect macrophages polarization.