title: Tumor-associated M2 macrophages in mycosis fungoides acquire immunomodulatory function by interferon alpha and interferon gamma.
abstract: BACKGROUND
  Tumor-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.
  
  
  OBJECTIVE
  To prove our hypothesis, we stimulated monocyte-derived M2 macrophages with IFN-α2a or IFN-γ and examined the mRNA expression of chemokines.
  
  
  METHODS
  By 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.
  
  
  RESULTS
  IFN-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.
  
  
  CONCLUSIONS
  Our data suggest one possible mechanism of the therapeutic effects of IFNs through TAMs for the treatment of advanced-stage MF.
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Sadanori
authors.initials: S
authors.lastname: Furudate
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: tfujimura1@mac.com.
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kakizaki
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hidaka
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Asano
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D018925:Chemokines; C573415:IFNG protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D007371:Interferon-gamma; D020782:Matrix Metalloproteinases; C100416:peginterferon alfa-2a
keywords: Chemokines; IFN-α; IFN-γ; Mycosis fungoides; Tumor-associated macrophages (TAMs)