Small molecule AZD4635 inhibitor of A_2AR signaling rescues immune cell function including CD103⁺ dendritic cells enhancing anti-tumor immunity.

ABSTRACT: Accumulation of extracellular adenosine within the microenvironment is a strategy exploited by tumors to escape detection by the immune system. Adenosine signaling through the adenosine 2A receptor (A_2AR) on immune cells elicits a range of immunosuppressive effects which promote tumor growth and limit the efficacy of immune checkpoint inhibitors. Preclinical data with A_2AR inhibitors have demonstrated tumor regressions in mouse models by rescuing T cell function; however, the mechanism and role on other immune cells has not been fully elucidated.

Methods

We report here the development of a small molecule A_2AR inhibitor including characterization of binding and inhibition of A_2AR function with varying amounts of a stable version of adenosin

SUBMITTER: Borodovsky A 

PROVIDER: S-EPMC7394305 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature