e13061 Background: We are now doing moncyte-derived dendritic cells (Mo-DCs)-based vaccine therapy for advanced cancer patients. It has been shown that hedgehog (Hh) pathway contributes to tumor progression. We know that microenviroment of tumor tissue is hypoxic condition. So, we hypothesized that hypoxic condition affects the functions of both Mo-DCs and tumor cells, and that Hh pathway contributes to their functional changes. Methods: Peripheral blood moncytes were cultured with GM-CSF and IL-4 for 7 days in a 1% O2 (hypo-DCs) or 20% O2 condition (normo-DCs). Human pancreatic cancer cells were cultured for 7 days in a 1% O2 (hypo-Tu) or 20% O2 condition (normo-Tu). Antigen presentation-related functions of Mo-DCs, including proliferation. Phagocytosis, IL-12 or VEGF secretions, migration, maturation, and allo T cell stimulating capacity were estimated by FACS, ELISA, random migration assay, Matrigel invasion assay, and 3H thymidine uptake. Expressions of Hh-related molecules were determined by real time PCR and immunofluorescent staining. A Smo inhibitor, cyclopamine, was used to inhibit Hh pathway. Results: (A) Mo-DCs: 1) Proliferation, migration, invasion, and allo T cell stimulating capacities in hypo-DCs were significantly lower than those in normo-DCs (p<0.01). 2) Phagocytosis and IL-12 or VEGF secretions in hypo-DCs were significantly higher (p<0.01). 3) The expressions of Hh- related molecules in hypo-DCs were significantly higher (p<0.01) 4) VEGF secretion in hypo-DCs was suppressed by cyclopamine. (B) Tumor cells: 1) Invasion and expression of Hh-related molecules in hypo-Tu were higher than those in normo-Tu (p<0.05). 2) Proliferation of hypo-Tu was lower than that of normo-Tu (p<0.05). 3) Increased invasion of hypo-Tu was suppressed by cyclopamine. Conclusions: Hypoxia environment at the tumor site induces the decreased of antigen-presentation abilities of Mo-DCs but induces increase of tumor cell invasion ability. Importantly, increased VEGF secretion of hypo-DCs was suppressed by cycolpamine. On the other hand, the increased invasionin hypo-Tu was decreased by cyclopamine. Thus, Hh pathway may be a valuable therapeutic target for DC-based immunotherapy. No significant financial relationships to disclose.