Pan‐cancer landscape of tumour endothelial cells pinpoints insulin receptor as a novel antiangiogenic target and predicts immunotherapy response

作者：Yongqiang Zheng, Yi‐Qian Pan, Kun Liao, Kai Yu, Qi‐Nian Wu, Yanxing Chen, Yuqing Deng, Hui‐Chuan Sun, Heng‐Ying Pu, Huai‐Qiang Ju, Rui‐Hua Xu, Zexian Liu · 发表于：Clinical and Translational Medicine · 年份：2023 · DOI：10.1002/ctm2.1501 · 被引用次数：7 · 研究领域：Angiogenesis and VEGF in Cancer、Cancer, Hypoxia, and Metabolism、Cancer Genomics and Diagnostics

Dear Editor, An in-depth study of tumour vasculature can reveal the mechanisms and consequences of dysregulated tumour angiogenesis and influence new treatment strategies.1-3 Here, we establish the first pan-cancer tumour endothelial cell (TEC) atlas, characterize the shared and cancer-specific phenotypes of TECs among diverse cancer types and explore novel antiangiogenic targets. Neo-angiogenesis is an important step in tumour development and metastasis to meet the metabolic remodelling requirements of tumours.4 Anti-angiogenic therapies have been devised to inhibit pathological angiogenesis, but their limited efficiency suggests that the urgency of more effective agents is needed.5 Deconstructing TECs at the single-cell level could assist the development of new antiangiogenic drugs, but the current studies are limited by the narrowed cancer types, small sample sizes, and the relatively low abundance of endothelial cells (ECs) in tissue.1-3 Currently, there is a continuous lack of systematic studies to resolve TECs across different cancer types and in large sample sizes. We established a pan-cancer TEC atlas from the large-scale data of a total of 1.24 million cells derived from 381 high-quality samples (Figure S1A–G and Tables S1 and S2). A detailed description of this atlas is shown in the Supporting Information. Up to 63 320 ECs comprising 37 367 TECs and 25 953 normal ECs (NECs) were aggregated (Figure 1A–C). Clusters were annotated according to the biological functions ...