Comparative cancer immunology: Inducing myeloid derived suppressor cells in vitro (P6092)

Abstract

Abstract Comparative oncology has broad applications in the development and optimization of novel therapeutics for cancer in both humans and animals. In this study, we developed in vitro tools to study canine myeloid derived suppressor cells (MDSCs). Previously, we have shown that tumor derived soluble factors (TDSFs) modified the function of a dendritic cell line. In this study, we investigated TDSF’s ability to induce MDSCs. TDSFs were generated from canine tumor cell lines and canine bone marrow precursors were differentiated in the presence of GM-CSF with or without TDSFs. We found that TDSFs dramatically increased the expression of CD11b+CADO48A+ (a canine MDSC marker akin to CD11b+Gr1+ MDSCs in mice) in cells between days 3-7 compared to controls with the highest percentage (40%) occurring on day 5 of differentiation. Day 5 TDSF-exposed cells suppressed the proliferation of responder immune cells. Similar results were found in companion studies using immunocompetent mice and murine in vitro TDSF-generated MDSCs. Taken together, these findings support that TDSFs can generate canine MDSCs in vitro that are similar to mouse MDSCs and that the in vitro generation of MDSCs mimics the immunosuppression seen with ex vivo derived MDSCs in humans and mice. These data have important implications both in understanding canine cancer immunology and for translational and therapeutic applications utilizing the dog as a model for human cancer.