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Figure 2. EVs can promote tumor progression of B cell malignancies through multiple mechanisms. The central orange cell represents a malignant B cell (e.g., MM, CLL, or DLBCL), and the small orange vesicles are the EVs released by the malignant B cell. These EVs can regulate T cell activation, osteoblast differentiation, the transformation of EC into CAF, the polarization of macrophages to M2, as well as be exchanged between cancer cells. MSCs can release EVs that directly affect B cell malignancies or take up EVs from B cell cancers. Activation of either MDSC or regulatory T cells can also suppress immune activation. Examples of intracellular mediators and extracellular cytokine release are shown. Bullets indicate proteins known to be transferred by EVs to recipient cells. Dashed arrows indicate the release of EVs by cells while solid arrows indicate the interaction of an EV with a target cell or release of a cytokine. Created in BioRender. Christian, S. (2025) https://BioRender.com/53cq8kd. Ag: Antigen; Akt: protein kinase B; APE1: apurinic/apyrimidinic endonuclease 1; ASmase: acid sphingomyelinase; BAFF: B-cell activating factor; CAF: cancer-associated fibroblast; CA1: carbonic anhydrase 1; CLL: chronic lymphocytic leukemia; DLBCL: diffuse large B-cell lymphoma; EC: endothelial cell; EVs: extracellular vesicles; FasL: Fas ligand; IL: interleukin; M2: M2 macrophages; MDSC: myeloid-derived suppressor cell; miR-125-5p: microRNA-125-5p; MM: multiple myeloma; MSCs: mesenchymal stromal cells; NFkB: nuclear factor kappa-light-chain-enhancer of activated B cells; NK cell: natural killer cell; P-Akt: phosphorylated Akt; P-ERK: phosphorylated extracellular signal-regulated kinase; PGC-1β: peroxisome proliferator-activated receptor γ coactivator 1β; P-STAT3: phosphorylated signal transducer and activator of transcription 3; RUNX2: runt-related transcription factor 2; TGF-β: transforming growth factor-β; Treg: regulatory T.