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.
针对肿瘤内皮细胞的治疗策略已被探索数十年，但始终未能达到理想疗效，部分原因在于对肿瘤患者间TEC异质性认知不足。我们整合了来自19种实体瘤类型的575例癌症患者的单细胞RNA测序数据，全面绘制了TEC表型多样性图谱。分析从泛癌视角揭示了此前未被充分认识的TEC组成与功能异质性。其中，CXCR4阳性尖端细胞和SELE阳性静脉内皮细胞分别代表了TEC最显著的促血管生成和促炎表型。它们展现出截然不同的空间分布模式：与相邻非肿瘤组织相比，肿瘤组织中CXCR4阳性尖端细胞显著增多，而SELE阳性静脉内皮细胞却呈现耗竭状态。这些功能与空间特性决定了二者对抗血管生成疗法及免疫疗法的响应存在差异。我们的整合性资源与发现为理解肿瘤脉管系统及临床干预开辟了新途径。
Pan-cancer integrative analyses dissect the remodeling of endothelial cells in human cancers
肿瘤(癌症)患者之家