CD39 and extracellular vesicles (EVs)
Cell membrane-expressed E-NTPDases include CD39 are also found in circulating microparticles in human plasma [114]. Tumor-derived EVs, including exosomes, microvesicles, and apoptotic bodies, have been shown to inhibit anti-tumor T-cells through CD39, CD73, and ADO signaling pathways [115, 116]. Zhang et al. showed that CD19+ EVs from B cells hydrolyzed ATP from chemotherapy-treated tumor cells into ADO via CD39 and CD73 vesicle-incorporated proteins, thus impairing CD8+T-cell responses [117]. In microenvironments containing CD39+CD73+ exosomes, CD73 is readily available to CD4+CD39+CD73negTregs for the production of immunosuppressive ADO[118]. Increased plasma microparticles (MP) expressing CD39 were observed in patients with liver injury, and plasma CD133 MP levels increased in a CD39-dependent manner during experimental acute liver injury [119]. CD4+T-cell-derived CD161+CD39+ and CD39+CD73+ MPs contain pro-inflammatory and anti-inflammatory information, respectively, and could serve as new biomarkers for diseases, such as rheumatoid arthritis[120]. Angioni et al. demonstrated that in response to pro-inflammatory cytokines, bone marrow mesenchymal stromal cells produce EVs that are enriched in TIMP-1,CD39, and CD73, which inhibit angiogenesis by targeting both extracellular matrix remodeling and endothelial cell migration [121]. Furthermore, CD39 expressed in EVs derived from endothelial cells influences thrombus progression [23, 122].