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Updated: Aug 10, 2025

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The ectonucleotidases CD39 and CD73 on T cells: The new pillar of hematological malignancy

Xuan Jiang1, Xiaofang Wu1, Yuxi Xiao1

  • 1Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.

Frontiers in Immunology
|February 13, 2023
PubMed

Hematological malignancy develops and applies various mechanisms to induce immune escape, in part through an immunosuppressive microenvironment. Adenosine is an immunosuppressive metabolite produced at high levels within the tumor microenvironment (TME). Adenosine signaling through the A2A receptor expressed on immune cells, such as T cells, potently dampens immune responses. Extracellular adenosine generated by ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5'-nucleotidase (CD73) molecules is a newly recognized 'immune checkpoint mediator' and leads to the identification of immunosuppressive adenosine as an essential regulator in hematological malignancies. In this Review, we provide an overview of the detailed distribution and function of CD39 and CD73 ectoenzymes in the TME and the effects of CD39 and CD73 inhibition on preclinical hematological malignancy data, which provides insights into the potential clinical applications for immunotherapy.

Keywords:
CD39CD73T cellshematological malignancyimmunotherapy

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