A2AR Antagonism with DZD2269 Augments Antitumor Efficacy of Irradiation in Murine Model.

ABSTRACT: Accumulated extracellular adenosine suppresses antitumor immunity via adenosine 2A receptor (A2AR). Blockade of A2AR with DZD2269 can inhibit phosphorylation of cAMP response element-binding protein mediated by adenosine analogue in vitro and in vivo. Irradiation can cause the release of adenosine and lead to a rapid increase in free extracellular adenosine in the tumour area. DZD2269, a novel A2AR Antagonism, induces incomplete antitumor responses in multiple syngeneic mouse tumour models. Combining DZD2269 with IR can induce a synergistic anticancer effect. IR increases the infiltration of various subtypes of T cells, including CD4+, CD8+ and Foxp3+ T cells, into the tumour area. Combining IR and DZD2269 improves the tumour immune microenvironment, leading to suppressed infiltration of regulatory T (Treg) cells and enhanced IFN-? expression by tumour-infiltrating lymphocytes. The results support the use of A2AR antagonism with DZD2269 as a therapeutic strategy for monotherapy or combination therapy with IR.

SUBMITTER: Huang J 

PROVIDER: S-EPMC7150468 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature