Consistent with previous reports of CD73 as a mediator of adenosine-driven immunosuppression and poor outcomes in multiple cancers [15,19,20], we found that NT5E expression correlates with HIF1α specifically in EAC but not in ESCC, associates with reduced overall survival, and increases with disease progression, establishing NT5E as a clinically relevant, EAC-specific vulnerability. Here, NT5E is linked to esophageal squamous cell carcinoma.