CD39

The CD39 ectonucleotidase triphosphate diphosphohydrolase 1 (Entpd1) represents a new promising target for cancer immunotherapy. CD39 is expressed on both regulatory T cells and tumor cells and plays a major role in promoting immunosuppression.

Background


An Overview of CD39

In 1982, Rowe et al first found a special molecular marker on the surface of B lymphocytes infected by EB virus, which was later named CD39. CD39 is an extracellular nucleotide diphosphate hydrolase 1 (NTPDase 1), which is widely expressed on human tissue cells. CD39 is a rate-limiting enzyme involved in the production of immunosuppressive adenosine. It was found that more than 90% of CD39 was expressed in monocytes, neutrophils and B lymphocytes, and about 6% of CD39 was expressed in T lymphocyte-grade NK cells. The main biological function of CD39 is to catalyze the hydrolysis of extracellular diphosphate nucleotides. At present, the catalytic hydrolysis of extracellular ATP into ADP and AMP has been studied. The immunosuppressive effect of CD39 is mediated by adenosine. Adenosine acts on the infiltrated immune cells in tumor to play an immunosuppressive effect.

Agonist of CD39

The expression of CD39 is mainly driven by the specific transcription factor Foxp3, other factors include interleukin-6 (IL-6), transforming growth factor-β(TGF-β) and hypoxia induced factor 1 (hypoxia inducible factor-1 (HIF-1). In animal experiments, almost all CD39 is expressed on the surface of Foxp3+Treg, and about 60% of CD73 is expressed on the surface of Foxp3+Treg, so on most of the Foxp3+Treg surfaces, CD39 and CD73 are co expressed.

CD39 and Diseases

CD39 is closely related to the occurrence and development of tumor as studies with statistical significance revealed. The expression of CD39 in many malignant tumors has been found to be significantly higher than that in normal tissues, such as kidney, lung, ovary, pancreas, thyroid and so on. A large number of studies have confirmed that targeting CD39 can inhibit the proliferation of tumor cells, reverse the function of immune cells, and enhance the immune effect. In recent years, the use of CD39 chemical inhibitors, monoclonal antibodies in vivo and in vitro experimental anti-tumor treatment has achieved a significant effect, providing a new way for anti-tumor therapy.

Reference:

Li Huijuan, Ye Liang, et al. A. (2018). Research Progress of CD39 in tumor immunity. Military Medical Journal of Southeast China. 20(1);45-49