title: Multiple Low Doses of 5-Fluorouracil Diminishes Immunosuppression by Myeloid Derived Suppressor Cells in Murine Melanoma Model.
abstract: BACKGROUND
  Melanoma progression and metastasis is suggested to be mediated by increased accumulation of myeloid derived suppressor cells. Various chemotherapeutic drugs such as 5-Fluorouracil in single low concentration have the capacity, at least in part, to reverse tumor progression by reducing myeloid derived suppressor cells-mediated immunosuppression.
  
  
  OBJECTIVE
  To assess whether multiple low doses of 5-fluorouracil could repress myeloid derived suppressor cells in low frequency and, in turn, could enhance anti-tumor responses and promote a more prolonged survival in a murine melanoma model.
  
  
  METHODS
  Fifty milligram per kilogram body weight dose of 5-Flourouracil was administered intraperitoneally 4 times with 3-day intervals to C57BL/6 mice after B16 melanoma tumor models were established. The frequency and suppressive functions of myeloid derived suppressor cells and induction of anti-tumor CD8+ T cells as well as tumor growth and survival were evaluated in drug treated and untreated mice.
  
  
  RESULTS
  Our results demonstrated that this therapeutic strategy increases the overall mice survival (p≤0.01) and induces melanoma-specific CD8+T cell immunity (p≤0.01) by reducing the frequency of myeloid derived suppressor cells (p≤0.01) as well as their immune suppressive functions (p≤0.05).
  
  
  CONCLUSIONS
  Altogether, our data suggest that 5-fluorouracil in multiple low regimens might be used to overcome tumor immunosuppression and improve the efficacy and outcome of anti-tumor immune responses in a mouse model.
authors.affiliation: Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, e-mail: Afshin_namdar@resident.mui.ac.ir.
authors.forename: Afshin
authors.initials: A
authors.lastname: Namdar
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Mirzaei
authors.forename: Farhad
authors.initials: F
authors.lastname: Jadidi-Niaragh
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Ashourpour
authors.forename: Maryam
authors.initials: M
authors.lastname: Ajami
authors.forename: Jamshid
authors.initials: J
authors.lastname: Hadjati
authors.forename: Abbas
authors.initials: A
authors.lastname: Rezaei
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002985:Clinical Protocols; D004195:Disease Models, Animal; D054796:Drug Dosage Calculations; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008545:Melanoma; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology*; D012867:Skin
chemical_list: D005472:Fluorouracil