PMN-MDSC and arginase are increased in myeloma and may contribute to resistance to therapy

<b>Objectives</b>: Despite improvement in overall response due to the introduction of the first-in-class proteasome inhibitor bortezomib (btz), multiple myeloma (MM) is still an incurable disease due to the immune-suppressive bone marrow (BM) environment. Thus, the authors aimed to identify the role of CD11b⁺CD15⁺CD14⁻HLA-DR⁻ granulocytic-like myeloid-derived suppressor cells (PMN-MDSC) in MM patients treated up-front with novel agents. <b>Methods</b>: In MM cell lines and primary cells derived by patients affected by MGUS and MM, we investigated sensitivity to bortezomib and lenalidomide in presence of Arg-1 and PMN-MDSC. <b>Results</b>: The authors found that PMN-MDSC and their function through increased arginase-1 (Arg-1) are associated with MM progression. When the authors assessed cell viability of the human myeloma cell lines MM1.s, OPM2 and U266 treated with 5–20 nM btz for 24 h in PMN-MDSC conditioned media, they disclosed that amount of Arg-1 and Arg-1 inhibition could affect btz sensitivity <i>in-vitro</i>. PMN-MDSC and Arg-1 were increased in peripheral blood of newly diagnosed MM patients compared to healthy subjects. PMN-MDSC and arginase were reduced after exposure to lenalidomide-based regimen but increased after btz-based treatment. <b>Conclusion</b>: In MM, Arg-1 is mainly expressed by PMN-MDSC. PMN-MDSC and Arg-1 are reduced <i>in vivo</i> after lenalidomide but not bortezomib treatment.