title: Prostate carcinoma cells LNCaP and glucan cooperate in induction of cytokine synthesis by dendritic cells: effect on natural killer cells and CD4+ lymphocytes activation.
abstract: BACKGROUND
  Glucan is an immunomodulating agent used for cancer therapy. We investigated the effects of glucan on immune cell response to prostate carcinoma.
  
  
  METHODS
  Dendritic cells (DC) were co-cultured with prostate carcinoma cells LNCaP and/or glucan, and maturation markers expression, cytokine release, and superoxide anion production were evaluated. Conditioned media from glucan-treated or untreated DC and/or LNCaP cultures were used to stimulate T lymphocytes and natural killer (NK) cells.
  
  
  RESULTS
  LNCaP promoted partial DC maturation and scarce IL-12 secretion. Glucan induced DC maturation but no IL-12 production by DC. However, glucan increased IL-12 release by DC co-cultured with LNCaP. Moreover, LNCaP enhanced IL-1β, IL-23, IL-6, and TNF-α secretion, but decreased superoxide anion production in glucan-stimulated DC. The NADPH oxidase inhibitor diphenyliodonium chloride (DPI) and the superoxide anion scavenger superoxide dismutase (SOD) reproduced this effect, but did not affect IL-12 secretion. Conditioned media of glucan-treated DC/LNCaP co-cultures activated IFN-γ production by NK cells and Th1/Th17 generation by CD4(+) lymphocytes, whereas media from DC/LNCaP co-cultured without glucan produced scarce NK and CD4(+) cells responses. Experiments performed with an IL-12-blocking antibody demonstrated that these effects arise from glucan-dependent regulation of IL-12 production by DC.
  
  
  CONCLUSIONS
  Glucan and LNCaP cooperate in induction of cytokine synthesis by DC. LNCaP enhance IL-1β, IL-23, IL-6, and TNF-α secretion by decreasing glucan-dependent NADPH oxidase activity, whereas glucan increases IL-12 production through NADPH oxidase-unrelated mechanisms. This cooperation is essential to elicit a substantial NK cells and CD4(+) lymphocytes activity, pointing out a potential relevance of glucan in prostate cancer therapy.
authors.affiliation: Section of General Pathology, Department of Pathology and Diagnostic, University of Verona, Verona, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Donini
authors.forename: Laura
authors.initials: L
authors.lastname: Marongiu
authors.forename: Emanuela
authors.initials: E
authors.lastname: Fontana
authors.forename: Stefano
authors.initials: S
authors.lastname: Dusi
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005936:Glucans / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D005936:Glucans; D007155:Immunologic Factors; D013481:Superoxides; D018664:Interleukin-12; D019255:NADPH Oxidases