Department of Oncology, VIB-KU Leuven Center for Cancer Biology, and KU Leuven, Leuven, Belgium.
Cancer Res. 2024 Nov 4;84(21):3502-3504. doi: 10.1158/0008-5472.CAN-24-3219.
In the first pan-cancer analysis of the tumor vasculature, Pan and colleagues profile nearly 200,000 endothelial cells (EC) and mural cells, identifying novel subclusters and cell states using consensus trajectory inference. They identify differentiation trajectories in vascular and lymphatic ECs and subtype the pericyte (PC) population. During sprouting angiogenesis, venous cells dedifferentiate and transition to capillary and, finally, arterial ECs. Capillary ECs transition via "three angiogenic stages" (SI-SIII), during which APLN+ TipS1 cells were identified as potential modulators of tumor-induced neovascularization and antiangiogenic therapy response. In lymphatic ECs, differentiation was inversely correlated between the lymphangiogenic (T1) and antigen-presenting (T2) trajectories, with T2 associated with a better prognosis. Although several PC clusters were identified, BASP1+ matrix-associated PCs were associated with APLN+ TipS1 cells and had a worse prognosis. These findings present transcriptional validation of previous experimental findings and serve as a resource to examine the tumor vascular microenvironment in detail.
在首个泛癌种的肿瘤血管分析中，Pan 及其同事对近 20 万内皮细胞（EC）和壁细胞进行了分析，使用共识轨迹推断方法鉴定了新的亚群和细胞状态。他们鉴定了血管和淋巴管内皮细胞的分化轨迹，并对周细胞（PC）群体进行了亚型分析。在血管生成芽生过程中，静脉细胞去分化并向毛细血管转化，最终向动脉 EC 转化。毛细血管 EC 通过“三个血管生成阶段”（SI-SIII）进行转化，在此期间，APLN+ TipS1 细胞被鉴定为肿瘤诱导的新生血管生成和抗血管生成治疗反应的潜在调节剂。在淋巴管内皮细胞中，淋巴管生成（T1）和抗原呈递（T2）轨迹之间呈负相关，T2 与更好的预后相关。尽管鉴定了几个 PC 簇，但 BASP1+基质相关 PC 与 APLN+ TipS1 细胞相关，并与预后不良相关。这些发现为之前的实验发现提供了转录验证，并可作为一个资源，用于详细检查肿瘤血管微环境。
