LRG1 Destabilizes Tumor Vessels and Restricts Immunotherapeutic Potency

摘要: Vascular dysfunction contributes to the pro-oncogenic tumor microenvironment and impedes delivery of therapeutics. Normalizing vasculature has therefore become a potential therapeutic objective. We previously reported that secreted glycoprotein, leucine-rich α-2-glycoprotein 1 (LRG1), formation pathogenic neovascularization. Here we show in mouse models cancer, Lrg1 is induced endothelial cells. demonstrate expression LRG1 impacts on progression as Lrg1 deletion or treatment with function-blocking antibody inhibited growth improved survival. Inhibition increased cell pericyte coverage vascular function resulting significantly enhanced efficacy cisplatin chemotherapy, adoptive T-cell therapy immune checkpoint inhibition (anti-PD1) therapy. With immunotherapy, led significant shift from being predominantly silent (cold) active (hot). drives abnormalization its represents novel effective means improving cancer therapeutics.