P-075: Myeloid derived suppressor cells are not elevated in monoclonal gammopathies

Abstract

<h3>Background</h3> The immunologically tolerant microenvironment may support a development of malignant multiple myeloma (MM) from precancerous monoclonal gammopathy of undetermined significance (MGUS) and blocks the efficacy of immunotherapy in existing MM as well. Myeloid derived suppressor cells (MDSC) represent heterogeneous group of cells with immunosuppressive activity and capability of promotion of tumor growth in MM. Their increased number and negative effect was described in MM but usually not in other monoclonal gammopathies (MGs). <h3>Aim</h3> Identification and enumeration of MDSC subsets in different MG subjects and comparison of their number with healthy controls. <h3>Methods</h3> Whole peripheral blood of 30 newly diagnosed and untreated MGs (2 MGUS, 7 MM with AL amyloidosis and 21 MM) and 13 healthy controls was used. Incubation with combination of MoAbs CD16/CD15/HLA-DR/CD14/CD45/CD11b/CD33/CD66b was done. Samples were analysed on BD FACSCanto II (BD Biosciences) after NH4Cl lysis and reanalysed with Infinicyt SW (Cytognos). <h3>Results</h3> Whole leukocytes were distributed into subpopulations using progressive gating strategy allowing detection of MDSC derived from granulocytes (G-MDSC) and monocytes (M-MDSC) with elimination of dendritic cells (DCs) and other contaminating cells (basophils etc.). There were found no differences in M- and G-MDSC relative and absolute count when compared whole MG group and controls. Even selection of MG with ≥95 % clonal plasma cells (PCs) or MGs with presence of circulating PCs or MGs with >30 g/l monoclonal Id protein did not show statistically different values of both MDSC subsets in comparison with control samples. The only statistically different value was decreased number of DCs in MGs. <h3>Conclusion</h3> Although elevated levels of MDSC in MM were previously published, this study did not prove it probably due to the different gating procedure. However, it was able to clearly define all leukocyte subsets in peripheral blood, thus only higher numbers of dublets may affect the final count of MDSC. Interestingly, low density neutrophils and tumor associated neutrophils should not be easily distinguish from MDSC, so their better characterization is needed in the future. The isolation and verification of MDSC immunosuppressive potential should be the next step in their analyses. Supported by MH CZ - DRO (FNBr, 65269705).