title: Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties.
abstract: OBJECTIVE
  Because of the labor-intensive and time-consuming conventional protocols for the generation of dendritic cells (DCs) as the most promising tools for anti-cancer therapy that enable the induction of a T-helper (Th)1-mediated anti-tumor immune response, the use of short-term protocols has been proposed. However, data on the applicability of such protocols in cancer immunotherapy are quite limited.
  
  
  METHODS
  We compared the phenotypic and functional capability of fast DCs (fDCs) differentiated for 24 h and then matured for 48 h with Poly (I:C), a strong Th1-promoting agent, with donor-matched conventional DCs (cDCs) differentiated for 5 days and matured likewise.
  
  
  RESULTS
  Of 12 donors tested, we identified seven whose monocytes failed to develop into immunogenic DCs through the use of fDC protocol, on the basis of incomplete downregulation of CD14, low expression of CD1a and macrophage-like morphology. Such fDCs have significantly lower expression of CD83, CD86, CCR7 and CD40, weaker allo-stimulatory Th1- and Th17-polarizing capacity caused by poor production of interleukin (IL)-12p70 and IL-23 and high production of IL-10, and prominent Th2-polarizing capacity, compared with donor-matched cDCs. Furthermore, such fDCs had tolerogenic properties as judged by higher expression of indolamine dioxigenase-3, IDO-1 and IL-1β and induction of a higher percentage of CD4(+)CD25(+)FoxP3(+) T cells. These findings correlated with increased transforming growth factor (TGF)-β production by fDC-primed CD3(+)T cells and their stronger anti-proliferative capacity.
  
  
  CONCLUSIONS
  We emphasize that although fDCs could probably be applied as an alternative to cDCs for cancer therapy, the fDC protocol should not be applied to donors whose DCs acquire tolerogenic capabilities.
authors.affiliation: Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Bojan
authors.initials: B
authors.lastname: Pavlović
authors.affiliation: Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia.
authors.forename: Sergej
authors.initials: S
authors.lastname: Tomić
authors.affiliation: Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Đokić
authors.affiliation: Institute for Medical Research, Military Medical Academy, University of Defence, Belgrade, Serbia.
authors.forename: Saša
authors.initials: S
authors.lastname: Vasilijić
authors.affiliation: Institute for Medical Research, Military Medical Academy, University of Defence, Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Vučević
authors.affiliation: Institute for Molecular Genetics and Genetic Engineering, Laboratory for Molecular Microbiology, University of Belgrade, Belgrade, Serbia.
authors.forename: Jovanka
authors.initials: J
authors.lastname: Lukić
authors.affiliation: Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia.
authors.forename: Alisa
authors.initials: A
authors.lastname: Gruden-Movsesijan
authors.affiliation: Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Ilić
authors.affiliation: Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia; Medical Faculty, University of Niš, Niš, Serbia.
authors.forename: Milan
authors.initials: M
authors.lastname: Marković
authors.affiliation: Medical Faculty of the Military Medical Academy, University of Defence, Belgrade, Serbia; Medical Faculty, University of Niš, Niš, Serbia. Electronic address: mjcolic@eunet.rs.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Čolić
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; C576710:IDO1 protein, human; C508609:IL10 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053759:Interleukin-23; D018950:Lipopolysaccharide Receptors; D016753:Interleukin-10; D018664:Interleukin-12; D011070:Poly I-C
keywords: Poly (I:C); T-regulatory cells; cancer immunotherapy; fast dendritic cells; tolerance