Targeting the A2AR in cancer; early lessons from the clinic
Stephen B. Willingham, Andrew Hotson, Richard A. Miller
Abstract
The immunosuppressive tumor microenvironment (TME) represents a challenge that all immunotherapies must overcome to enable a robust and durable anti-tumor response. One of the dominant mechanisms of immunosuppression in the TME is hypoxia and the generation of extracellular adenosine [1]. Pioneering work from Drs Ohta and Sitkovsky demonstrating that adenosine signaling through the adenosine 2A receptor (A2AR) inhibits T cells has led to the development of several agents designed to inhibit the production or downstream signaling of adenosine [2••,3••]. This review will focus on the safety, efficacy, and biomarkers associated with A2AR antagonists in clinical development.
Topics & Concepts
AdenosineAdenosine receptorTumor microenvironmentImmunosuppressionMedicineAdenosinergicAdenosine A2A receptorCancer researchImmune systemReceptorImmunologyInternal medicineAgonistAdenosine and Purinergic SignalingImmune Cell Function and InteractionPhagocytosis and Immune Regulation