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

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

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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 of575 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.

tumor endothelial cellpan-cancersingle-cell RNA-seqimmunotherapy

Jinhu Li、Dongfang Wang、Fei Tang、Xinnan Ling、Wenjie Zhang、Zemin Zhang

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Biomedical Pioneering Innovation Center(BIOPIC),School of Life Sciences,Peking University,Beijing 100871,China

Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China

National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaBeijing Municipal Science and Technology Commission

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2024

10.1093/nsr/nwae231

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ISSN：
年,卷(期)：2024.11(9)