Ex vivo nicotine stimulation augments the efficacy of therapeutic bone marrow-derived dendritic cell vaccination

PURPOSE: To explore the preventive and therapeutic antitumor effects of nicotine-treated immature dendritic cells (imDC).

EXPERIMENTAL DESIGN: 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.