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

Abstract

228 Background: Immune-based therapies have begun to demonstrate efficacy in GI oncology. However immune-suppressor mechanisms have been described which interfere with host anti-tumor immunity. Myeloid derived suppressor cells (MDSCs) constitute a heterogenous population known to be increased in patients with GI cancer. MDSCs inhibit the host anti-tumor immune response, limiting the effectiveness of both immune and non-immune treatments. Characterization of MDSCs 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) lysates from both healthy adults and patients with advanced hepatocellular, colorectal and pancreatic cancer. Antibodies used for subtype characterization: anti-CD14, anti-CD15, anti-HLA-DR, anti-CD33, anti-CD11b. Functional studies performed to confirm MDSC status included thymidine proliferation assay on sorted cell populations. Results: Samples were obtained from 20 patients with advanced GI cancer and healthy volunteers and processed accordingly. Based on published data the following MDSC subtypes were analyzed: A) CD14+, HLA-DR−/low; B) CD15+,CD14-CD33+CD11b+.The frequency of each subset is shown in the table below. Functional studies will also be presented. Conclusions: Characterization of MDSCs in humans has been difficult with heterogeneous and often contradictory phenotype classification. In addition, there is considerable variability depending on which component of the blood is analyzed and how the sample is processed. This study confirms the increase in both MDSC populations in patients with GI cancer. [Table: see text]