Fig. 3

The immunosuppressive tumor microenvironment in MM. The TME present in BM creates a unique milieu that favors MM immune evasion and promotes disease progression. The tumor-immune niche and the tumor-microenvironment is implicated in malignant cell protection against anti-tumor therapy. The BM niche, composed of a cellular compartments, e.g., stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells, an acellular compartment, e.g., extracellular matrix and liquid milieu, e.g., cytokines, growth factors, and chemokines, promote the homing differentiation, migration, proliferation, survival, and drug resistance of malignant PCs. MM cells inhibit the development of an effective anti-tumor immune responses through defects in T cell function, ineffective antigen presentation, reduced phagocytic capacity, natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive proinflammatory cytokines. Immune cells including plasmacytoid dendritic cells and macrophages further trigger tumor cell proliferation, survival, and drug resistance. Novel therapies in MM target not only the tumor cell but also the BM and TME