CD39-CD73-adenosine effects in Sézary syndrome

In this issue of Blood, Yakymiv et al(1) provide evidence that malignant CD4+ T-cells derived from patients with Sezary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL), express high levels of the CD39 and CD73 ectonucleotidases, which may contribute to an immunosuppressive microenvi-ronment. Treatment of advanced stages of CTCLs remains challenging, reflecting a low rate of durable remissions despite recent approval of several targeted therapies, such as brentuximab and mogamulizumab. Unlike mature nodal T-cell malignancies, CTCLs derived from skin-homing memory CD4+ T-cells have very high tumor mutational burden due to ultraviolet radiation,2 but responses to checkpoint inhibition remain modest.3 This level of response reflects the difficulty of enhancing T-cell immune responses in T-cell malignancy, and so an under-standing of the tumor microenvironment in CTCLs remains a critical need.