Clinical significance of defective dendritic cell differentiation in cancer

Defective dendritic cell (DC) function has been described previously in can cer patients and tumor-bearing mice. It can be an important factor in the e scape of tumors from immune system control, However, the mechanism and clin ical significance of this phenomenon remain unclear. Here, 93 patients with breast, head and neck, and lung cancer were investigated. The function of peripheral blood and tumor draining lymph node DCs was equally impaired in cancer patients, consistent with a systemic rather than a local effect of t umor on DCs, The number of DCs was dramatically reduced in the peripheral b lood of cancer patients. This decrease was associated with the accumulation of cells lacking markers of mature hematopoietic cells. The presence of th ese immature cells was closely associated with the stage and duration of th e disease. Surgical removal of tumor resulted in partial reversal of the ob served effects. The presence of immature cells in the peripheral blood of c ancer patients was closely associated with an increased plasma level of vas cular endothelial growth factor but not interleukin 6, granulocyte macropha ge colony-stimulating factor, macrophage colony-stimulating factor, interle ukin 10, or transforming growth factor-beta and was decreased in lung cance r patients receiving therapy with antivascular endothelial growth factor an tibodies. These data indicate that defective DC function in cancer patients is the result of decreased numbers of competent DCs and the accumulation o f immature cells. This effect may have significant clinical implications.