Although, this finding does not rule out the possibility that targeting tumor (stem) cell-expressed Dll4 may contribute to the overall anti-tumor activity of Dll4 blockade in other settings, it suggests that the anti-tumor activity of Dll4 blockade in the employed RCC PDX model is dependent on targeting Dll4 in the tumor stroma, and the lack of tumor growth-promoting autocrine Dll4-Notch tumor cell signaling in this model. Here, DLL4 is linked to renal cell carcinoma.