CAFs constitute the prominent CD73hi population in human CRCs and two CD73−murine tumor models, including a modified CRC. High CAF abundancy in CRC tissues correlates strongly with elevated CD73 activity and poor prognosis. CAF-CD73 expression is enhanced via an ADO-A2B receptor-mediated feed-forward circuit triggered by tumor cell death, which enforces the CD73 checkpoint. The gene discussed is NT5E; the disease is neoplasm.