Murine prostate cancer inhibits both In vivo and In vitro generation of dendritic cells from bone marrow precursors

BACKGROUND. There is increasing evidence to suggest that dendritic cells (DC) are functionally impaired in tumor bearing hosts. However there is little or no data on the effects of murine prostate cancer (CaP) on DC generation from bone marrow precursors. METHODS. Flow cytometry, mixed leukocyte reactions (MLR), and immunohistochemical analyses were used to characterize DC in CaP. RESULTS. DC generated in the presence of CaP cell lines RM1 and the cell line C2 from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse in a Transwell system expressed significantly lower levels of DC differentiation markers. This effect was confirmed when TK-neo-transfected RM1 cells were directly added to DC cultures and eliminated 5 days later using gancyclovir (GCV). Furthermore, co-incubation of DC with CaP cells resulted in a decrease in the stimulatory capacity of DC to induce T cell proliferation in the MLR assay. These results were further confirmed in vivo in two different murine models of CaP: i) DC generated from mice intrafemorally injected with TK-neo-transfected RMI cells; and ii) in DC generated from TRAMP mice. CONCLUSIONS. The generation and function of DC are significantly suppressed in the CaP microenvironment in both in vivo and in vitro murine models. (C) 2003 Wiley-Liss, Inc.