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.

成人T细胞白血病/淋巴瘤（ATLL）患者的预后极差，部分原因是其免疫抑制状态。大多数ATLL患者的白血病细胞表型与Treg相似，提示ATLL细胞本身具有免疫抑制功能。在这项研究中，我们检测到ATLL细胞上CD39的表达，尤其是侵袭性亚型的CD39表达频繁。CD39和CD73将细胞外三磷酸腺苷（ATP）转化为腺苷，这是Tregs免疫抑制的关键因素。在体外培养中，CD39 ⁺ ATLL细胞和正常Tregs迅速将胞外ATP转化为AMP，AMP39受到CD39抑制剂的干扰，在CD39敲除的MJ细胞系中被否定。共培养的CD4 ⁺ / CD8 ⁺的增殖正常的T细胞被CD39 ⁺ MJ细胞抑制，但未被CD39敲除MJ细胞抑制。具有稳定的CD39诱导作用的EG7-OVA T细胞系耗尽了补充的ATP，但没有模拟。当将这些细胞系皮下移植到小鼠侧腹中时，在模拟移植的肿瘤中进行腹膜给予Poly（I：C）可以将肿瘤大小减小到1/3，而在CD39诱导的肿瘤中则没有。总的来说，我们发现ATLL细胞高表达CD39，我们的结果表明，这有助于ATLL细胞通过细胞外ATPDase-腺苷级联逃避抗肿瘤免疫。这些发现将指导ATLL治疗的未来临床策略。