CREB1 and neoplasm: PD-1/PD-L1 axis regulation: 1 In CD8+ T cells, Adora2b-cAMP-PKA activates CREB, which directly binds the CRE site (TGACGTCA) on the PD-1 promoter; PKA inhibition reduces PD-1 expression by 92% (97); 2 In tumor cells, Adora2b stabilizes HIF-1α via cAMP, promoting PD-L1 transcription; Adora2b knockdown reduces PD-L1 expression by 64% (96).