Adult T-cell leukemia/lymphoma (
ATLL) patients have an extremely poor prognosis, partly due to their immunosuppressive state. The majority of
ATLL patients have leukemic cells with phenotype similar to Tregs, prompting suggestions that
ATLL cells themselves have immunosuppressive functions. In this study, we detected CD39 expression on
ATLL cells, particularly frequent on aggressive subtypes. CD39 and CD73 convert extracellular
adenosine triphosphate (
ATP) into
adenosine, a key player in Tregs' immunosuppression. In vitro culture, both CD39+
ATLL cells and normal Tregs converted rapidly extracellular
ATP to
AMP, which was disturbed by CD39 inhibitors, and was negated in the CD39 knockout MJ cell line. The proliferation of cocultured CD4+/CD8+ normal T cells was suppressed by CD39+ MJ cells, but not by CD39 knockout MJ cells. Supplemented
ATP was exhausted by an EG7-OVA T-cell line with stable CD39 induction, but not by mock. When these cell lines were subcutaneously transplanted into murine flanks,
Poly(I:C) peritoneal administration reduced
tumor size to 1/3 in mock-transplanted
tumors, but not in CD39 induced
tumors. Overall, we found that
ATLL cells express CD39 at a high rate, and our results suggest that this helps
ATLL cells escape antitumor immunity through the extracellular ATPDase-
Adenosine cascade. These findings will guide future clinical strategies for
ATLL treatment.