High-grade glioma (HGG) is highly angiogenic, but antiangiogenic therapy has transient clinical benefit in only a fraction of patients. Vascular regulators of these heterogeneous responses remain undetermined. We found up-regulation of Sox7 and down-regulation of Sox17 in tumor endothelial cells (tECs) in mouse HGG. Sox7 deletion suppressed VEGFR2 expression, vascular abnormality, hypoxia-driven invasion, regulatory T cell infiltration, and tumor growth. Conversely, Sox17 deletion exacerbated these phenotypes by up-regulating Sox7 in tECs. Anti-VEGFR2 antibody treatment delayed tumor growth by normalizing Sox17-deficient abnormal vessels with high Sox7 levels but promoted it by regressing Sox7-deficient vessels, recapitulating variable therapeutic responses to antiangiogenic therapy in HGG patients. Our findings establish that Sox7 promotes tumor growth via vessel abnormalization, and its level determines the therapeutic outcome of VEGFR2 inhibition in HGG. In 189 HGG patients, Sox7 expression was heterogeneous in tumor vessels, and high Sox7 levels correlated with poor survival, early recurrence, and impaired vascular function, emphasizing the clinical relevance of Sox7 in HGG.

高度神经胶质瘤（HGG）具有高度血管生成作用，但抗血管生成治疗仅在一小部分患者中具有短暂的临床益处。这些异质性反应的血管调节剂尚未确定。我们在小鼠HGG的肿瘤内皮细胞（tEC）中发现了Sox7的上调和Sox17的下调。Sox7缺失抑制了VEGFR2的表达，血管异常，缺氧驱动的侵袭，调节性T细胞浸润和肿瘤生长。相反，Sox17缺失通过上调tEC中​​的Sox7加剧了这些表型。抗VEGFR2抗体通过使Sox17缺陷的高Sox7水平异常血管正常化而延迟了肿瘤的生长，但通过使Sox7退化而促进了它的生长。血管缺损，概括了HGG患者对抗血管生成治疗的各种治疗反应。我们的发现确定，Sox7通过血管异常促进肿瘤生长，其水平决定了HGG中VEGFR2抑制的治疗结果。在189例HGG患者中，Sox7在肿瘤血管中的表达异质，并且高的Sox7水平与不良的存活率，早期复发和血管功能受损相关，强调了Sox7在HGG中的临床意义。