Clayton Heathcock Lectureship: Studies Related to the ATP-Adenosine Pathway

Seminar | February 5 | 11 a.m.-12 p.m. | 120 Latimer Hall

 Terry Rosen, Arcus Biosciences

 College of Chemistry

Tumor cell death induced by hypoxia or chemotherapy releases large amounts of ATP (adenosine triphosphate) into the extracellular environment. ATP is rapidly converted to AMP (adenosine monophosphate) which, in turn, is converted by hypoxia-induced CD73 into adenosine (ADO). ADO suppresses immune responses, including those of T cells, NK cells and dendritic cells through activation of adenosine receptors A2aR and A2bR. Exhausted T cells and NK cells express high levels of several immune checkpoint (IC) proteins, including PD-1 and TIGIT. Combined expression of IC proteins with CD73 or A2aR/A2bR in multiple tumor types presents an opportunity for novel combinatorial therapies. In this talk, we will discuss the biology of the ATP-adenosine pathway, the discovery of highly potent and selective inhibitors of CD73 and combined antagonists of A2aR/A2bR, the properties of these molecules and early data from their clinical investigation.
