CD39 belongs to the ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase) family. It is a surface-expressed enzyme involved in the hydrolysis of the extracellular ATP, a proinflammatory metabolite, and ADP. CD39 enzymatic activity results in the generation of ADP and AMP. In turn CD73 converts AMP into the immunosuppressive adenosine. The latter is known to bind to the adenosine A2a receptor (A2aR or ADORA2A), which is one of the so called ‘checkpoint blockades’, because it plays an important part in regulating responses to inflammation and restricts inflammatory tissue damage. Expression of CD39 is present in a broad set of tissue types, with spleen, thymus, lung and placenta having this protein expressed constitutively. It is primarily found on endothelial cells and immune cell populations. Increased expression of CD39 has been shown in some solid tumors, such as colorectal cancer (CRC), head and neck cancer, and pancreatic cancer, as well as in chronic lymphocytic leukemia.