Involvement of the CD39/CD73/adenosine pathway in T-cell proliferation and NK cell-mediated antibody-dependent cell cytotoxicity in Sézary syndrome

TO THE EDITOR:

Extracellular adenosine (eAdo) has been identified as a potent inhibitor of antitumor immune responses and enhancer of tumor survival. Two ectonucleotidases, CD39 and CD73, are involved in the generation of eAdo from adenosine triphosphate (ATP). Numerous studies have demonstrated their active role in promoting solid tumor outgrowth and spreading but also in inhibiting the antitumor immune response. Indeed, accumulation of eAdo was detected in solid tumors, and binding of eAdo to its receptors (A2AR) expressed at the surface of immune cells provides an immunosuppressive signal on effector T, natural killer (NK), and NKT cells, macrophages/dendritic cells, and neutrophils.¹ In addition, signaling through A2AR upregulates a number of anti-inflammatory molecules and the activity of regulatory T cells, leading to a long-lasting immunosuppressive environment.^2,3 Accordingly, the use of A2AR antagonists has demonstrated promising efficacy in the treatment...