Targeting CD73 to augment cancer immunotherapy

Abstract

CD73 (ecto-5'-nucleotidase) is a novel immunoinhibitory protein that plays a key role for tumor growth and metastasis. Its main function is to convert extracellular ATP to immunosuppressive adenosine in concert with CD39 in normal tissues to limit excessive immune response. However, tumors take advantage of the CD73-mediated adenosinergic mechanism to protect them from immune attack. In particular, inducible expression of CD73 along with other adenosinergic molecules on both cancer cells and host cells sustains immunosuppressive tumor microenvironment by affecting multiple aspects of the immune response. Owing to its multifaceted capacity to tumor promotion as an emerging immune checkpoint, CD73 is an ideal therapeutic target for cancer treatment especially in combination with conventional therapy and/or other immune checkpoint inhibitors. In this review, we will discuss the roles of CD73 on tumor and immune cells and will highlight the therapeutic value of CD73 for combination therapy.