Tumor-associated M2 macrophages in mycosis fungoides acquire immunomodulatory function by interferon alpha and interferon gamma

•We previously reported that the TAMs stimulated by stromal factors produce the chemokines that affect the formation of CTCL.•In this report, we investigated the immunomodulatory effects of IFN-a and IFN-g on M2 macrophages by performing DNA microarray analysis.•Our data suggested one of the possible mechanisms of the therapeutic effects of IFN-a and IFN-g through TAMs for the treatment of advanced-stage MF.

BackgroundTumor-associated M2 macrophages (TAMs) produce chemokines that affect the formation of cutaneous T-cell lymphoma (CTCL) by stromal factors. Since IFNs are an effective treatment for advanced-stage mycosis fungoides (MF), we hypothesized that IFNs might modulate M2 macrophages.ObjectiveTo prove our hypothesis, we stimulated monocyte-derived M2 macrophages with IFN-α2a or IFN-γ and examined the mRNA expression of chemokines.MethodsBy using a microarray, we selected a series of chemokines and MMPs that were strongly connected with the IL-4 stimulation. Then, we investigated the effects of IFN-α2a and IFN-γ on these chemokines.ResultsIFN-α2a and IFN-γ decreased the expression and production of CCL17 and CCL18 and increased those of CXCL10 and CXCL11. Moreover, the subcutaneous administration of IFN-α2a increased the CXCL11-producing cells in the lesional skin of patients with advanced MF.ConclusionOur data suggest one possible mechanism of the therapeutic effects of IFNs through TAMs for the treatment of advanced-stage MF.