Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC)

Granulocytic-Myeloid-derived suppressor cells (G-MDSC) are increased inMultiple Myeloma (MM) patients but the mechanisms of G-MDSC generation are stillunknown. There are many evidences of the role of mesenchymal stem cells (MSC)in promoting MM cell growth, survival and drug-resistance. We here used a specificexperimental model in vitro to evaluate the ability of MSC to induce G-MDSC. Wefound that although MSC derived from healthy donors (HD), MGUS and MM wereable to generate the same amount of MDSC, only MM-MSC-educated G-MDSCexhibited suppressive ability. In addition, in comparison with MSC derived from HD,MM-MSC produce higher amount of immune-modulatory factors that could beinvolved in MDSC induction. Compared to G-MDSC obtained from co-culture modelswith MSC from healthy subjects, both MGUS and MM-MSC-educated G-MDSC showedincrease of immune-modulatory factors. However, only MM-MSC educated G-MDSC 1)up-regulated immune-suppressive factors as ARG1 and TNFα, 2) expressed higherlevels of PROK2, important in angiogenesis and inflammatory process, and 3) showedability to digest bone matrix.Our data demonstrate that MM-MSC are functionally different from healthysubjects and MGUS-MSC, supporting an evolving concept regarding the contributionof MM-MSC to tumor development and progression.