The inhibition of endothelial DLL4-NOTCH1 signaling by 2'-hydroxyflavanone enhances anti-PD-1 therapy in melanoma.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics; however limited patient responses necessitate combination strategies to improve therapeutic efficacy. Among potential combination partners, drugs targeting DLL4-NOTCH1 signaling pathway-a critical regulator of vascular function-show promise as angiogenesis modulators, but their clinical development have been hindered by safety concerns. To address this challenge, we adopted a novel approach by screening natural compounds with a long history of human consumption.