Figure 1.

The proposed mechanisms of action of lenalidomide in multiple myeloma include immune modulation (A); interference with tumor microenvironment interactions (B); and direct antitumor effects (C). (A) Immunomodulation by lenalidomide includes T cell co-stimulation, suppression of Tregs, increased production of Th1 cytokines, and activation of NK and NKT cells. (B) Lenalidomide mediates disruption of myeloma cell-microenvironment interactions via several mechanisms including antiangiogenesis, anti-inflammatory effects, antiosteoclastogenic properties, modulation of cytokine production, and downregulation of adhesion molecules. (C) IMiDs also exert direct effects on myeloma cells via cell cycle arrest and induction of apoptosis.

Abbreviations: T reg, regulatory T cell; BMSCs, bone marrow stromal cells; APC, antigen-presenting cell; NK cells, natural killer cells; NKT cells, natural killer T cells; ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor; RANKL, receptor activator of nuclear factor kappa-B ligand; bFGF, basic fibroblast growth factor; TGF-β, transforming growth factor-β; IGF-1, insulin-like growth factor 1; TNF-α, tumor necrosis factor α; IL-6, interleukin-6.