BACKGROUND: Adenosine accumulated in the tumor microenvironment functions as an immune-modulating factor, exerting immunosuppressive actions via adenosine A2A/A2B receptor (A2AR/A2BR) in various immune cell types. CD73, a key enzymatic regulator responsible for adenosine production, is frequently overexpressed in diverse cancers, and its overexpression is associated with reduced responsiveness to conventional anti-cancer drug treatments such as chemotherapy, radiation therapy, targeted therapy, or immunotherapy. Despite numerous therapeutic applications of IL-2 in cancer immunotherapy, the relationship between the CD73-adenosine axis and IL-2-based immunotherapy remains largely unexplored. METHODS: To evaluate the effect of CD73 blockade on IL-2 signaling of CD8 RESULTS: IL-2-induced increase in proliferation of CD8 CONCLUSIONS: GI-αCD73/IL-2v bispecific protein is a novel and potent immunocytokine with significant antitumor immunity through cis-binding on CD8