Immunoregulatory activity of adenosine and its role in human cancer progression

The adenosinergic pathway plays an important role in cancer progression. Aside from regulating functions of tumor cells and tissue cells present in the tumor microenvironment, extracellular adenosine is an autocrine or paracrine factor with powerful immunoregulatory activity. Adenosine signaling downregulates functions of most immune effector cells but enhances expansion and activity of immune cells responsible for suppression of anti-tumor immune responses. Adenosine is critical for limiting potential tissue-destructive effects of activated immune cells. It also facilitates tumor escape from the immune control. This review illustrates the involvement of adenosine and its four receptors, A1R, A2AR, A2BR and A3R, in the complex regulation of cellular and molecular cross talk that contributes to cancer progression. It also considers the potential of therapeutics targeting the adenosinergic pathway for benefiting cancer patients.