Dendritic cells and type I and II interferon production in the local microenvironment of sinonasal tumors

Abstract

The subpopulations of dendritic cells and their functional potential determined by endogenous interferon status in tumor microenvironment is an important stage in tumor-specific T-lymphocytes effector reactions development. In this regard, understanding the patterns of sinonasal neoplasms immune cells changes is important in the context of the search for biomarkers of the tumor process which may open up new opportunities for targeted therapy. This study is the first to provide a comparative description of dendritic cells subsets and the type I and type II interferon production in patients with malignant and benign sinonasal tumors.Tumor tissue from 30 patients with neoplasms – main group (15 patients with malignant tumors and 15 patients with inverted papilloma) and biopsy material of the mucous membrane from 15 patients with polypous rhinosinusitis (comparison group) were used. Tumor-infiltrating immune cells were isolated from tissue using automated and enzymatic cell dissociation. The surface and intracellular cells phenotype was assessed using monoclonal antibodies and flow cytometry. The production of α- and γ-interferons was determined by enzyme-linked immunosorbent assay. Statistical data analysis was proceeded in Statistica 10.0.An increase of tumor-infiltrating myeloid dendritic cells number was found in patients with malignant tumors as compared to control group what correlated with the stage of the pathological process (R = -0.67; p = 0.01). There was an increase in both myeloid and plasmacytoid dendritic cells in the neoplasm tissue in patients with inverted papilloma relative to the comparison group. The microenvironment of malignant growth was characterized by an increase in α- and γ-interferons production in combination with a pronounced decrease in IFNγ-producing T cells percent while a decrease in both intracellular and extracellular production of γ-interferons was detected in tumor tissue of patients with inverted papilloma as compared with control group.In patients with sinonasal tumors changes in dendritic cells subpopulations as well as a decrease in the reserve capacity of γ-interferon synthesis were revealed what may characterize the involvement of these mechanisms in the formation of the antitumor immune response failure and requires further research to establish their pathogenetic role.

Keywords

• dendritic cells
• interferons
• tumor microenvironment
• sinonasal neoplasms
• inverted papilloma
• polypous rhinosinusitis