Adenosine and adenosine receptors in colorectal cancer

CD39 (nucleoside triphosphate diphosphohydrolase) and Ecto-5-nucleotidase (CD73) have been recognized as important factors mediating various pathological and physiological responses in the tumor microenvironment. Elevated expression of CD73 and CD39 is correlated with the over-production of adenosine in the tumor region. This increase is associated with an immunosuppressive state in the tumor site that enhances various tumor hallmarks such as metastasis, angiogenesis, and cell proliferation. Adenosine promotes these behaviors through interaction with four adenosine receptors, including A3R, A2BR, A2AR, and A1R. Signaling of these receptors reduces the function of immune effector cells and enhances the expansion and function of tumor-associated immune cells. Several studies have been shown the important role of adenosine/CD73/CD39/ARs axis in the immunopathogenesis of colorectal cancer. These findings imply that components of this axis can be considered as a worthy target for colorectal cancer immunotherapy. In this review, we summarized the role of CD73/CD39/adenosine/ARs in the immunopathogenesis of colorectal cancer.