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Figure 4. Other microenvironment components. (A) Inflammatory mesenchymal stromal cells (iMSCs): IL-1, TNF-alfa secreted by myeloid cells, cytotoxic T cells and NK cells and DAMPs deriving from tumor cells induce inflammatory phenotype of stromal cells. In turn, iMSC support tumor development through secretion of IL-6, LIF, CCL2 among other cytokines. iMSC simultaneously recruit and modulate immune cells, primarily myeloid cells. (B) osteoclasts: upregulation of Gal-9, CD200, HVEM, CD200, PD-L1, RANK in osteoclasts with secretion of IDO induce immuno-suppression; osteoclasts also produce OPN, IL-6, BAFF and APRIL that support MM survival. (C) Exosomes: BM cells in MM compared to healthy donors showed lower levels of miRNA-15a and increased levels of pro-tumoral Il-6, fibronectin, and CCL-2.