MYELOID-DERIVED SUPPRESSOR CELLS ACCUMULATE AND ARE IMMUNOSUPPRESSIVE IN PATIENTS WITH MULTIPLE MYELOMA — The Association Specialists
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MYELOID-DERIVED SUPPRESSOR CELLS ACCUMULATE AND ARE IMMUNOSUPPRESSIVE IN PATIENTS WITH MULTIPLE MYELOMA (330)

Tulita Liyadipitiya 1 2 , James Favaloro 1 , Ross Brown 1 , Shihong Yang 1 , Hayley Suen 1 2 , Narelle Woodland 2 , Najah Nassif 2 , John Gibson 1 , P Joy Ho 1 , Douglas Joshua 1
  1. Institute of Haematology, Royal Prince Alfred Hospital , Camperdown, NSW, Australia
  2. School of Medical & Molecular Biosciences, University of Technology Sydney, Sydney, NSW, Australia

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells with a consensual phenotype of CD33+CD11b+HLA-DRlow/-. Monocytic (M-MDSC) and granulocytic (G-MDSC) subpopulations express CD14+ and CD15+, respectively. It has been proposed that these cells regulate the immune system during the pathogenesis of cancer by the production of immunosuppressive enzymes and the induction of T-regulatory cells (Tregs).

AIM: This project aimed to investigate MDSCs in patients with multiple myeloma (MM) and determine their function in vitro.

METHODS: Whole blood, peripheral blood mononuclear (PBMC) and bone marrow (BM) cells were obtained, after consent, from excess clinical samples and analysed by flow cytometry (BD FACS Canto II). MDSC were separated by pre-enrichment using magnetically activated cell sorting (MACS), and further sorted using fluorescent activated cell sorting (BD FACS Aria II). Autologous PBMCs were then co-cultured at a 1:1 ratio with isolated MDSCs.

RESULTS: G-MDSC were significantly increased (U=78.5; p= 0.04) in the blood of MM patients (n=25, mean= 9.2%) compared to healthy age matched controls (n=11, mean= 2.1%) and even higher (U=0.0; p=0.0001) in patients with active disease (n=10, mean= 48.6%). There was a significantly higher proportion (t=3.5; p=0.008) of G-MDSC in matched BM than PB (n=9, mean= 59.3% and 23.8% respectively), regardless of disease stage or treatment. Functionally, MDSC sorted from MM patients (n=7) induced a significantly greater proportion of Tregs (mean=5.8% before vs. 8.7% after co-culture; p= 0.005) than age matched controls (n=4, mean=4.2% before vs. 4.8% after co-culture; p= 0.03). Furthermore, MDSC sorted from MM patients (n=6) inhibited autologous T-cell proliferation (mean= 28.6% inhibition) at a greater level than MDSC sorted from healthy donors (n=4, mean= 15.1%), although this did not reach statistical significance.

CONCLUSION: G-MDSCs were expanded in patients with MM, inhibited T-cell proliferation and induced additional Tregs. Understanding MDSCs will assist with optimising future immunotherapy programs.