Comparative analysis of myeloid-derived suppressor cell (MDSC) subsets in patients with gastrointestinal (GI) malignancies.

Abstract

10566 Background: Immunotherapy represents a potential new treatment option for patients with cancer. Myeloid derived suppressor cells (MDSCs) constitute a heterogenous cell population, which inhibit the host anti-tumor immune response, limiting the effectiveness of both immune and non-immune treatments. MDSC are known to be increased in patients with GI cancer. Characterization of MDSC in humans has been difficult with heterogeneous phenotype classification. Differences in processing are also potentially important. The aim of this study was to perform a comparative analysis of MDSC subsets in patients with GI cancer. Methods: Fluorescence activated cell sorting (FACS) analysis was performed on PBMC and whole blood (WB) from healthy adults (N=44) and patients with GI cancer (N=41). MDSC subsets were enumerated using the following antibodies: anti-CD14; anti-CD15; anti-HLA-DR; anti-CD33; anti-CD11b; 7-AAD. Suppressor function of MDSC subsets was tested using FACS sorted MDSC subpopulations co-cultured with CD3/CD28-stimulated autologous effector cells. Proliferation and IFN-g were measured. Results: The frequencies of Monocytic (Def: CD14+, HLA-DR -/low) and Granulocytic (Def: CD15+,CD14-CD33+CD11b+) MDSC are shown in the table below. Monocytic MDSC were increased in the blood of patients (vs control; P<.0001) and frozen (vs fresh PBMC; P<.05). While CD15+ cells were increased in cancer patients we did not find an increase in granulocytic MDSC. Functional studies will also be presented. Conclusions: Monocytic MDSC are more frequent in patients with advanced GI cancer compared to healthy volunteers. An increase in this population was also found in WB and frozen PBMC compared to fresh PBMC reflecting the need for homogenous preparation in studies evaluating this population in humans. While CD15+CD14- cells were also increased in cancer patients we did not find an increase in CD14-CD15+CD33+CD11b+ cells. [Table: see text]