Zev Wainberg, MD, University of California Los Angeles, Los Angeles, CA, describes the rationale behind CD39 antagonism as an immunotherapy for multiple cancers. CD39 is a rate-limiting enzyme in the conversion of ATP to immunomodulatory adenosine. It is thought that CD39 antagonism can prevent the accumulation of adenosine and stabilize pro-inflammatory extracellular ATP to restore antitumor immunity. CD39 will likely serve as a synergistic immunotherapy in combination with immune checkpoint blockade via PD-1 inhibition with pembrolizumab or nivolumab among others. This interview took place at the American Association for Cancer Research Annual Meeting 2022 in New Orleans, LA.