Pan-cancer integrative analyses dissect the remodeling of endothelial cells in human cancers  

作　　者：Jinhu Li Dongfang Wang Fei Tang Xinnan Ling Wenjie Zhang Zemin Zhang 

机构地区：[1]Biomedical Pioneering Innovation Center(BIOPIC),School of Life Sciences,Peking University,Beijing 100871,China [2]Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China

出　　处：《National Science Review》2024年第9期123-138,共16页国家科学评论（英文版）

基　　金：supported by the National Key Research and Development Program of China(2023YFF1204700,2023YFF1204704,2023YFF1204702 and 2022YFC2505005);the National Natural Science Foundation of China(81988101,62203019,31991171,91959000,92159305 and 92259205);the Beijing Municipal Science and Technology Commission(Z221100007022002).

摘　　要：Therapeutics targeting tumor endothelial cells(TECs)have been explored for decades,with only suboptimal efficacy achieved,partly due to an insufficient understanding of the TEC heterogeneity across cancer patients.We integrated single-cell RNA-seq data of 575 cancer patients from 19 solid tumor types,comprehensively charting the TEC phenotypic diversities.Our analyses uncovered underappreciated compositional and functional heterogeneity in TECs from a pan-cancer perspective.Two subsets,CXCR4^(+)tip cells and SELE^(+)veins,represented the prominent angiogenic and proinflammatory phenotypes of TECs,respectively.They exhibited distinct spatial organization patterns,and compared to adjacent non-tumor tissues,tumor tissue showed an increased prevalence of CXCR4^(+)tip cells,yet with SELE^(+)veins depleted.Such functional and spatial characteristics underlie their differential associations with the response of anti-angiogenic therapies and immunotherapies.Our integrative resources and findings open new avenues to understand and clinically intervene in the tumor vasculature.

关 键 词：tumor endothelial cell pan-cancer single-cell RNA-seq immunotherapy 

分 类 号：R73[医药卫生—肿瘤]