title: Interferon alpha-induced reduction in the values of myeloid-derived suppressor cells in melanoma patients.
abstract: OBJECTIVE
  Interaction between tumor cells and host's immunoregulatory cells in creation of microenvironment that supports tumor progression is the focus of numerous investigations in recent years. Myeloid-derived suppressor cells (MIDSCs) are heterogeneous population of immature dendritic cells, macrophages and granulocytes. In cancer patients, these cells accumulate in tumor microenvironment, tumor-draining lymph nodes, peripheral blood and the liver and their numbers correlate with the stage of the disease and the metastatic disease. The aim of the study was to investigate the effect of interferon alpha on MDSCs percentage in peripheral blood of melanoma patients.
  
  
  METHODS
  The interferon treated melanoma patients were given subcutaneously interferon alpha, in optimal dose, for a period of at least 6 months before the analysis. Blood samples were collected from the melanoma patients (n=91) and the age/sex matched healthy controls (n=8). The following anti-human monoclonal antibodies were used for immunostaining: anti-CD15-FITC, anti-CD33-PE, anti-CD45-ECD, anti-HLA-DR PE/Cy5, anti-CD14-FITC, anti-CD16-PE and anti-CD11b-PE.
  
  
  RESULTS
  Comparison of myeloid- derived suppressor cells values in the stage 2 melanoma patients with and without interferon alpha therapy did not show a significant difference. When we compared the MDSCs values in the patients within stage 3 melanoma, we found a significant difference in granulocytic subset values between the interferon alpha-treated and the untreated group. Comparison of values of all suppressor cells populations between the interferon alpha-treated patients and healthy controls showed a significant increase in suppressor cells percentage in the melanoma patients. The granulocytic and total MDSCs values were significantly lower in the interferon alpha treated melanoma patients with progression in comparison with untreated patients with stable disease.
  
  
  CONCLUSIONS
  We confirmed that interferon alpha effect in stage 3 melanoma patients was reduction in MDSCs percentage. We also found an unexpected bounce back of these suppressor cells levels, many months after the discontinuation of interferon alpha therapy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Stanojević
authors.forename: Milomir
authors.initials: M
authors.lastname: Gavević
authors.forename: Milena
authors.initials: M
authors.lastname: Jović
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Mijugković
authors.forename: Radog
authors.initials: R
authors.lastname: Zevević
authors.forename: Lidija
authors.initials: L
authors.lastname: Zolotarevski
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Jauković
authors.forename: Milica
authors.initials: M
authors.lastname: Rajović
authors.forename: Marijan
authors.initials: M
authors.lastname: Novaković
authors.forename: Ivana
authors.initials: I
authors.lastname: Binić
authors.forename: Danilo
authors.initials: D
authors.lastname: Vojvodić
mesh_terms: D002450:Cell Communication / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D018450:Disease Progression; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000276:immunology; D016898:Interferon-alpha / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D008875:Middle Aged; D022423:Myeloid Cells / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha