Notably, cordycepin augmented anti-PD1 efficacy in vivo via a suppressive effect on NK-A2AR and NK-A2BR expression and enhanced the inhibitory effects of anti-PD1 on A2AR and A2BR expression in splenic macrophages and intratumoral NK cells, indicating a novel pathway to clarify the biological function of cordycepin in colon cancer. Here, ADORA2A is linked to colonic neoplasm.