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The Journal of Immunology, 2000, 164: 1269-1276.
Copyright © 2000 by The American Association of Immunologists

Tumors Promote Altered Maturation and Early Apoptosis of Monocyte-Derived Dendritic Cells1

Sylvia M. Kiertscher2,*, Jie Luo*, Steven M. Dubinett*,{dagger},{ddagger} and Michael D. Roth*,{dagger}

* Division of Pulmonary and Critical Care Medicine and {dagger} Jonsson Comprehensive Cancer Center, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095; and {ddagger} West Los Angeles Veterans Affairs Medical Center, Los Angeles, CA 90073

Tumors produce a number of immunosuppressive factors that block the maturation of CD34+ stem cells into dendritic cells (DC). We hypothesized that tumors might also interfere with the maturation and/or function of human monocyte-derived DC. In contrast to stem cells, we found that CD14+ cells responded to tumor culture supernatant (TSN) by increasing expression of APC surface markers, up-regulating nuclear translocation of RelB, and developing allostimulatory activity. Although displaying these characteristics of mature DC, TSN-exposed DC lacked the capacity to produce IL-12, did not acquire full allostimulatory activity, and rapidly underwent apoptosis. The effects of TSN appeared to be specific for maturing DC, and were not reversed by Abs against known DC regulatory factors including IL-10, vascular endothelial growth factor, TGF-ß, or PGE2. Supernatants collected from nonmalignant 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.




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