Correlating A2AR engagementand downstream signaling was possible thanks to the phosphorylationmeasurement of the downstream effector CREB for all the optimizedNAMs (with IC50 < 200 nM and full % inhibition of receptoractivity), clearly showcasing the potential of A2AR allostericmodulation as a novel approach for efficient and safer cancer immunotherapies. This evidence concerns the gene ADORA2A and cancer.