Tumor stromal-derived molecules (TDMs: PGE2, IL-10, TGF-, VEGF etc) impact the tumor immune response by stimulating the proliferation of transformed cells, enhancing angiogenesis, and altering the functionality of the infiltrating immune cells including dendritic cells (DCs).Recently we have shown that monocyte-derived DCs activated by Toll-like receptor (TLR) agonists can be directed either to secrete high level of both IL-12 and IL-23 or IL-23 alone.These DCs can induce either a Thl or a Thl7 T helper response respectively.We hypothesize that these DCs will be influenced by the tumor micro-environment, and therefore evaluated the effects of TDMs on human monocyte-derived DCs.TLR agonist matured DCs secreted high levels of IL-12 (15-114ng/ml), highly expressed CD80, CD86, CD83, MHCⅠ, MHCⅡ, CD40, and strongly polarized na(i)ve CD4+T cells toward a Th1 type response.Addition ofTDM IL-10 or PGE2 prior to maturation of DC significantly inhibited DC IL-12 production by 80-95 % (1-10ng/ml) and 50-90 % (2-34ng/ml) respectively.However, when the same TDM were added after the maturation with TLR reagents, only marginal inhibition was seen.