title: Efficient generation of highly immunocompetent dendritic cells from peripheral blood of patients with hepatitis C virus-related hepatocellular carcinoma.
abstract: OBJECTIVE
  Immunotherapy using dendritic cells (DCs) is a promising cancer therapy. The success of this therapy depends on the function of induced DCs. However, there has been no consensus on optimal conditions for DC preparation in vitro for immunotherapy of hepatocellular carcinoma (HCC) patients. To address relevant issues, we evaluated the procedures to induce DCs that efficiently function in hepatitis C virus (HCV)-related HCC.
  
  
  METHODS
  We studied immunological data from 14 HCC patients. The DC preparation and the surface markers were assessed by flow cytometric analysis. Four different additional activation stimuli (Method I, medium alone; Method II, with OK-432; Method III, with IL-1β+IL-6+TNF-α; Method IV, with IL-1β+IL-6+TNF-α+PGE2) were tested and the functions of DCs were confirmed by examination of the ability of phagocytosis, cytokine production and allogeneic mixed lymphocyte reaction (MLR).
  
  
  RESULTS
  The numbers of DCs induced and their cytokine production ability were not different between healthy controls and HCC patients. T-cell stimulatory activity of DCs in MLR was significantly lower in HCC patients than in healthy controls. The maturation of DCs with OK-432 boosted production of cytokines and chemokines, such as IL-2, IL-12p70, IFN-γ, TNF-α, IL-13 and MIP1α, and restored T-cell stimulatory activity of DCs in MLR.
  
  
  CONCLUSIONS
  The clinically approved compound OK-432 is a candidate for highly immunocompetent DC preparation and may be considered as a key drug for immunotherapy of HCV-related HCC patients.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kitahara
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Eishiro
authors.initials: E
authors.lastname: Mizukoshi
authors.affiliation: Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Nakamoto
authors.affiliation: Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan. Electronic address: skaneko@m-kanazawa.jp.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007121:Immunocompetence / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology* / Q000821:virology; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007378:Interleukins; C493277:MAPKAP1 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Cancer; Cytokine; HCV; Immunotherapy