title: Ex vivo nicotine stimulation augments the efficacy of therapeutic bone marrow-derived dendritic cell vaccination.
abstract: OBJECTIVE
  To explore the preventive and therapeutic antitumor effects of nicotine-treated immature dendritic cells (imDC).
  
  
  METHODS
  First, bone marrow-derived imDCs were stimulated with nicotine in vitro, and nicotinic acetylcholine receptor, costimulator molecules, chemokine receptor, and endocytosis ability of imDCs were detected by flow cytometry. Second, the DC-dependent antigen-specific T-cell proliferation, CTL priming, and interleukin-12 secretion were determined by flow cytometry, enzyme-linked immunospot assay, and ELISA, respectively. Finally, preventive and therapeutic antitumor effects of such imDCs were determined by i.p. transfer against tumor challenge or implantation in mice.
  
  
  RESULTS
  Nicotine could up-regulate expression of nicotinic acetylcholine receptor, costimulatory molecules, such as CD80, CD86, and CD40, adhesion molecule CD11b, and chemokine receptor CCR7 and enhance endocytosis ability of imDCs. In addition, nicotine could promote imDC-dependent CTL priming and interleukin-12 secretion in vitro. Most importantly, systemic transfer of ex vivo nicotine-stimulated imDCs could reveal preventive and therapeutic effect on tumor development.
  
  
  CONCLUSIONS
  Ex vivo nicotine stimulation can significantly improve the efficacy of imDCs for adaptive therapy of cancer and nicotine-treated imDCs may be considered as a potential candidate for preventive and therapeutic tumor vaccination.
authors.affiliation: The National Laboratory for Oncogenes and Related Genes, Cancer Institute of Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Feng Guang
authors.initials: FG
authors.lastname: Gao
authors.forename: Da Fang
authors.initials: da F
authors.lastname: Wan
authors.forename: Jian Ren
authors.initials: JR
authors.lastname: Gu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D019496:Cancer Vaccines; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation*; D004705:Endocytosis / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
chemical_list: D015703:Antigens, CD; D019496:Cancer Vaccines; C515371:Ccr7 protein, mouse; D016207:Cytokines; D018722:Nicotinic Agonists; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D011978:Receptors, Nicotinic; D009538:Nicotine