A paper from the Immunogenetics group demonstrates that the extracellular form of the NAD biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) is a critical element in the induction of an immunosuppressive and tumor-promoting microenvironmen

NAMPT is the rate-limiting enzyme in NAD biosynthesis. In the extracellular compartment it exhibits cytokine/adipokine-like properties. Extracellular NAMPT (eNAMPT) levels are increased in various metabolic and inflammatory diseases as well as in tumors, rendering this pleiotropic molecule a novel player in tumor/host cross-talk. In this paper published in Blood http://www.ncbi.nlm.nih.gov /pubmed/25368373, Valentina Audrito and colleagues from the Immunogenetics Unit show that NAMPT levels are increased in CLL lymphocytes and that eNAMPT production is induced upon activation of the leukemic cells. In the CLL microenvironment, eNAMPT is an important element in inducing monocyte polarization to M2 macrophages secreting immunosuppressive and tumor promoting cytokines and reducing T cell responses. These effects are independent of the enzymatic activity of NAMPT, as inferred from the use of an enzymatically inactive mutant. Overall, these results reveal that eNAMPT is a critical element in the induction of an immunosuppressive and tumor-promoting microenvironment of CLL.