Impairment of dendritic cells (DC), the most effective activators of anti-cancer immune responses, is one mechanism for defective anti-tumor immunity, but the causes of DC impairment are incompletely understood. We evaluated the association of impaired DC differentiation with angiogenesis-associated molecules D-dimer, vascular endothelial growth factor (VEGF), urokinase plasminogen activator and plasminogen activator inhibitor (PAI-1) in peripheral blood from 41 patients with lung, breast, and colorectal carcinoma. Subsequently, we studied the effect of administration of the anti-VEGF antibody (bevacizumab) on DC maturation and function in vivo. Compared with healthy volunteers, cancer patients had a bias towards the immunoregulatory DC2, had deficits in DC maturation after overnight in vitro culture, and had a significant increase in immature myeloid cell progenitors of DC (0.50 +/− 0.31% vs. 0.32 +/− 0.16%, respectively, p=0.011). A positive correlation was found between the percentage of DC2 and PAI-1 (R=0.50) and between immature myeloid cells and VEGF (R=0.52). Bevacizumab administration to cancer patients was associated with a decrease in the accumulation of immature progenitor cells (0.39 +/− 0.30 % vs. 0.27 +/− 0.24 %, p=0.012) and induced a modest increase in the DC population in peripheral blood (0.47 +/− 0.23 % vs. 0.53 +/− 0.30 %). Moreover, anti-VEGF antibody treatment enhanced allo-stimulatory capacity of DC and T cell proliferation against recall antigens. These data suggest that DC differentiation is negatively associated with VEGF levels and may be one explanation for impaired anti-cancer immunity, especially in patients with advanced malignancies.