Li Jinhu, Wang Dongfang, Tang Fei, Ling Xinnan, Zhang Wenjie, Zhang Zemin
Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
Natl Sci Rev. 2024 Jul 11;11(9):nwae231. doi: 10.1093/nsr/nwae231. eCollection 2024 Sep.
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, tip cells and 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 tip cells, yet with 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.
针对肿瘤内皮细胞(TECs)的治疗方法已经探索了数十年,但仅取得了次优疗效,部分原因是对癌症患者中TECs异质性的了解不足。我们整合了来自19种实体瘤类型的575名癌症患者的单细胞RNA测序数据,全面描绘了TECs的表型多样性。我们的分析从泛癌角度揭示了TECs中未被充分认识的组成和功能异质性。两个亚群,即顶端细胞和静脉细胞,分别代表了TECs突出的血管生成和促炎表型。它们表现出不同的空间组织模式,与相邻的非肿瘤组织相比,肿瘤组织中顶端细胞的比例增加,而静脉细胞减少。这种功能和空间特征是它们与抗血管生成疗法和免疫疗法反应的不同关联的基础。我们的综合资源和发现为理解和临床干预肿瘤血管系统开辟了新途径。