Direct mechanisms operated by myeloma cells include: 1) IL-6 production (39, 40) which prevents MDSC differentiation and promotes MDSC accumulation and activation via the STAT3 signaling pathway (41); 2) the induction of Mcl-1, an anti-apoptotic protein sustaining MDSC survival (42); 3) the secretion of galectin-1 that targets CD304 on MDSC and enhances their immune suppressive capacity (43); 4) the production of chemokine ligand 5 (CCL5) and macrophage migration inhibitory factor (MIF) (44). This evidence concerns the gene NRP1 and plasma cell myeloma.