Abstract
The immunosuppressive effect of adenosine in the microenvironment of a tumor is well established. Presently, researchers are developing approaches in immune therapy that target inhibition of adenosine or its signaling such as CD39 or CD73 inhibiting antibodies or adenosine A2A receptor antagonists. However, numerous enzymatic pathways that control ATP-adenosine balance, as well as understudied intracellular adenosine regulation, can prevent successful immunotherapy. This review contains the latest data on two adenosine-lowering enzymes: adenosine kinase (ADK) and adenosine deaminase (ADA). ADK deletes adenosine by its phosphorylation into 5′-adenosine monophosphate. Recent studies have revealed an association between a long nuclear ADK isoform and an increase in global DNA methylation, which explains epigenetic receptor-independent role of adenosine. ADA regulates the level of adenosine by converting it to inosine. The changes in the activity of ADA are detected in patients with various cancer types. The article focuses on the biological significance of these enzymes and their roles in the development of cancer. Perspectives of future studies on these enzymes in therapy for cancer are discussed.
Highlights
Academic Editor: Alan PremCancer therapy based on the modulation of immune processes, such as immune checkpoint blockade and adoptive cell therapy, has achieved significant results
It was established that CD39, which hydrolyzes adenosine triphosphate (ATP) into adenosine diphosphate (ADP)/adenosine monophosphate (AMP), and CD73, which mediates the subsequent breakdown of AMP into adenosine, plays a key role in the development of tumors [5]
The studies experimentally and clinically confirmed the effectiveness of CD39, CD73-blocking antibodies, and antagonists of adenosine A2A receptor as agents that decrease the levels of adenosine and block their signaling [5]
Summary
Cancer therapy based on the modulation of immune processes, such as immune checkpoint blockade and adoptive cell therapy, has achieved significant results. It was established that CD39, which hydrolyzes ATP into adenosine diphosphate an end product in the transmethylation reaction: transmethylation (ADP)/adenosine monophosphate (AMP), and CD73, which mediates the subsequentreactions include the transfer breakdown Their expression and activity are elevated in the tumor tissue and blood and are often product, S-adenosylhomocysteine (SAH), is cleaved by SAH hydrolase (SAHH) into adenosine associated with clinical signs of the disease and unfavorable prognosis in some cancers and homocysteine. It was established that CD39, which hydrolyzes ATP into adenosine diphosphate (ADP)/adenosine monophosphate (AMP), and CD73, which mediates the subsequent breakdown of AMP into adenosine, plays a key role in the development of tumors [5] Their expression and activity are elevated in the tumor tissue and blood and are often associated with clinical signs of the disease and unfavorable prognosis in some cancers [6–11]. Perspectives of further studies on these enzymes for the therapy of oncologic diseases are discussed
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