| Summary: | Abstract Background The aim of this study is to evaluate the prognostic impact of myeloid-derived suppressor cells (MDSCs) in multiple myeloma (MM) in the context of autologous stem cell transplantation (ASCT). Methods Peripheral blood samples were collected for measuring monocytic (M-) MDSCs (CD14posHLA-DRlow/neg) and early-stage (E-) MDSCs (LinnegHLA-DRnegCD33posCD11bpos) before and after ASCT. Clinical outcomes following ASCT differed according to the frequency of each MDSC phenotype. Results In the pre-ASCT analyses, lower M-MDSCs (<median) but not E-MDSCs were associated with a longer time to progression (TTP), whereas both MDSC phenotypes post-ASCT did not have a role in TTP. Both MDSC phenotypes pre-ASCT but not post-ASCT similarly suppressed in vitro autologous T and natural killer T cell proliferation. Importantly, pre-ASCT M-MDSCs more strongly inhibited the in vitro cytotoxic effect of melphalan compared with pre-ASCT E-MDSCs. Transcriptome analysis of each isolated MDSC subtype showed that expression of osteoclastic differentiation factors, particularly colony-stimulating factor 1 receptor (CSF1R), was significantly increased in M-MDSCs pre-ASCT. Finally, blockade of CSF1R substantially recovered the melphalan-induced cytotoxicity reduced by pre-ASCT M-MDSCs. Conclusions Our data demonstrate that pre-ASCT M-MDSCs are correlated with poor clinical outcomes after ASCT through reduced cytotoxicity of melphalan. We propose that targeting CSF1R on these cells may improve the results of ASCT in MM.
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