Tumor exosomes inhibit differentiation of bone marrow dendritic cells (49.14)

Abstract The production of exosomes by tumor cells has been implicated in tumor-associated immune suppression. Here we show that, in mice, exosomes produced by TS/A murine mammary tumor cells target CD11b+Gr-1+ myeloid precursors in the bone marrow in vivo and that this is associated with an accumulation of myeloid precursors in the spleen. Moreover, we demonstrate that TS/A exosomes block differentiation of murine myeloid precursor cells into dendritic cells in vitro. Addition of tumor exosomes at day 0 led to a complete block of differentiation into dendritic cells, whereas addition at later time points was less effective. Similarly, exosomes produced by human breast tumor cells inhibited differentiation of human monocytes in vitro. The levels of IL-6 and phosphorylated Stat3 were elevated 12 h after tumor exosome stimulation of murine myeloid precursors, and tumor exosomes were less effective in inhibiting differentiation of bone marrow cells isolated from IL-6 knockout mice. These data suggest that tumor exosome-mediated induction of IL-6 plays a role in blocking bone marrow dendritic cell differentiation.