Adenosine pathway enzymes

The adenosine pathway enzymes represent a group of ectonucleotidases and metabolic enzymes, most notably Ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and 5'-nucleotidase (CD73), that regulate the conversion of extracellular adenosine triphosphate (ATP) into adenosine [1, 4]. In a healthy physiological state, this pathway maintains a balance between pro-inflammatory ATP and anti-inflammatory adenosine to protect tissues from excessive immune-mediated damage [11, 16]. However, in the tumor microenvironment, hypoxia and cell death lead to high levels of extracellular ATP, which these enzymes rapidly convert into adenosine, creating a potent immunosuppressive milieu [3, 15]. This accumulation of adenosine inhibits the effector functions of T cells and natural killer cells while recruiting regulatory immune cells, thereby allowing tumors to evade the immune system [2, 5]. Consequently, the adenosine pathway has emerged as a significant therapeutic target in oncology, with various inhibitors of CD39 and CD73 currently in clinical trials, often as combination therapies with checkpoint inhibitors [11, 15]. Beyond cancer, enzymes like adenosine deaminase (ADA) and adenosine kinase (ADK) maintain physiological adenosine levels, with dysregulation linked to inflammatory diseases, cardiovascular disorders, and neurological conditions such as epilepsy [10, 12, 17].

Other names

Adenosinergic pathwayCD39-CD73-adenosine axisPurinergic signaling pathwayEctonucleotidase pathwayAdenosine metabolic pathway

Inhibition of the enzymatic conversion of pro-inflammatory ATP to immunosuppressive adenosine by targeting CD39 and CD73, or the enhancement of adenosine degradation via adenosine deaminase to restore anti-tumor immunity and modulate inflammatory responses [1, 4, 11].