title: Low Noncytotoxic Concentrations of 5-Fluorouracil Have No Adverse Effects on Maturation and Function of Bone Marrow-Derived Dendritic Cells in vitro: A Potentially Safe Adjuvant for Dendritic Cell-Based Cancer Therapy.
abstract: BACKGROUND
  Low, noncytotoxic concentrations of various chemotherapeutic drugs like 5-fluorouracil (5-FU) induce antitumor immune responses by selectively depleting tumor-induced immunosuppressive cells, and could therefore be used in combination with dendritic cell (DC) vaccines in order to enhance their immunotherapeutic efficacy. However, the likely negative influences of low, noncytotoxic doses of 5-FU on bone marrow-derived (BM)-DCs in vitro have not yet been investigated.
  
  
  METHODS
  The effects of low, noncytotoxic concentrations of 5-FU on mouse BM-DC differentiation and maturation markers (CD11c, MHC class II and CD80) as well as antigen-presenting capacity and cytokine production (IL-12p70 and IL-10) have been assessed.
  
  
  RESULTS
  Different low doses of 5-FU had no significant effect on the expression of DC differentiation and maturation or on costimulatory markers (p = 0.5). Furthermore, suboptimal doses of 5-FU did not affect the immunostimulatory functions of DCs such as antigen presentation (p = 0.6) and cytokine production (p = 0.9).
  
  
  CONCLUSIONS
  These data suggest that low doses of 5-FU have no adverse effects on DC maturation and function, and the efficacy of DC-based cancer immunotherapy may be greatly enhanced by combining it with suboptimal doses of 5-FU.
authors.affiliation: Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Namdar
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Mirzaei
authors.forename: Morteza
authors.initials: M
authors.lastname: Hafezi
authors.forename: Najmeh
authors.initials: N
authors.lastname: Khosravianfar
authors.forename: Nasim
authors.initials: N
authors.lastname: Kheshtchin
authors.forename: Reza
authors.initials: R
authors.lastname: Mirzaei
authors.forename: Jamshid
authors.initials: J
authors.lastname: Hadjati
authors.forename: Abbas
authors.initials: A
authors.lastname: Rezaei
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D019496:Cancer Vaccines; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000628:therapy
chemical_list: D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; C556062:IL10 protein, mouse; D016753:Interleukin-10; D018664:Interleukin-12; D005472:Fluorouracil