Tumors promote altered maturation and early apoptosis of monocyte-derived dendritic cells

Tumors produce a number of immunosuppressive factors that block the maturat ion of CD34(+) stem cells into dendritic cells (DC), We hypothesized that t umors might also interfere with the maturation and/or function of human mon ocyte-derived DC. In contrast to stem cells, we found that CD14(+) cells re sponded to tumor culture supernatant (TSN) by increasing expression of APC surface markers, up-regulating nuclear translocation of RelB, and developin g allostimulatory activity. Although displaying these characteristics of ma ture DC, TSN-exposed DC lacked the capacity to produce IL-12, did not acqui re full allostimulatory activity, and rapidly underwent apoptosis. The effe cts of TSN appeared to be specific for maturing DC, and were not reversed b y Abs against known DC regulatory factors including IL-10, vascular endothe lial growth factor, TGF-beta, or PGE(2). Supernatants collected from nonmal ignant cell sources had no effect on DC maturation. The altered maturation and early apoptosis of monocyte-derived DC may represent another mechanism by which tumors evade immune detection.