Glioblastoma is the most common primary brain tumor and has a dismal prognosis. The development of central necrosis represents a tipping point in the evolution of these tumors that foreshadows aggressive expansion, swiftly leading to mortality. The onset of necrosis, severe hypoxia and associated radial glioma expansion correlates with dramatic tumor microenvironment (TME) alterations that accelerate tumor growth. In the past, most have concluded that hypoxia and necrosis must arise due to “cancer outgrowing its blood supply” when rapid tumor growth outpaces metabolic supply, leading to diffusion-limited hypoxia. However, growing evidence suggests that microscopic intravascular thrombosis driven by the neoplastic overexpression of pro-coagulants attenuates glioma blood supply (perfusion-limited hypoxia), leading to TME restructuring that includes breakdown of the blood–brain barrier, immunosuppressive immune cell accumulation, microvascular hyperproliferation, glioma stem cell enrichment and tumor cell migration outward. Cumulatively, these adaptations result in rapid tumor expansion, resistance to therapeutic interventions and clinical progression. To inform future translational investigations, the complex interplay among environmental cues and myriad cell types that contribute to this aggressive phenotype requires better understanding. This review focuses on contributions from intratumoral thrombosis, the effects of hypoxia and necrosis, the adaptive and innate immune responses, and the current state of targeted therapeutic interventions.

胶质母细胞瘤是最常见的原发性脑肿瘤，预后不佳。中央坏死的发展代表了这些肿瘤发展的转折点，预示着侵略性扩张，迅速导致死亡。坏死、严重缺氧和相关放射状胶质瘤扩张的发生与加速肿瘤生长的显着肿瘤微环境 (TME) 改变相关。过去，大多数人得出的结论是，当肿瘤快速生长超过代谢供应时，“癌症供血不足”必然会出现缺氧和坏死，从而导致扩散限制性缺氧。然而，越来越多的证据表明，由促凝剂的肿瘤过度表达驱动的微观血管内血栓形成会减弱神经胶质瘤的血液供应（灌注限制性缺氧），导致 TME 重组，包括血脑屏障破坏、免疫抑制性免疫细胞积累、微血管过度增殖、胶质瘤干细胞富集和肿瘤细胞向外迁移。累积起来，这些适应导致肿瘤快速扩张、对治疗干预的抵抗和临床进展。为了为未来的转化研究提供信息，需要更好地理解环境线索和导致这种侵袭性表型的无数细胞类型之间的复杂相互作用。本综述重点关注肿瘤内血栓形成、缺氧和坏死的影响、适应性和先天免疫反应以及靶向治疗干预的现状。微血管过度增殖、胶质瘤干细胞富集和肿瘤细胞向外迁移。累积起来，这些适应导致肿瘤快速扩张、对治疗干预的抵抗和临床进展。为了为未来的转化研究提供信息，需要更好地理解环境线索和导致这种侵袭性表型的无数细胞类型之间的复杂相互作用。本综述重点关注肿瘤内血栓形成、缺氧和坏死的影响、适应性和先天免疫反应以及靶向治疗干预的现状。微血管过度增殖、胶质瘤干细胞富集和肿瘤细胞向外迁移。累积起来，这些适应导致肿瘤快速扩张、对治疗干预的抵抗和临床进展。为了为未来的转化研究提供信息，需要更好地理解环境线索和导致这种侵袭性表型的无数细胞类型之间的复杂相互作用。本综述重点关注肿瘤内血栓形成、缺氧和坏死的影响、适应性和先天免疫反应以及靶向治疗干预的现状。为了为未来的转化研究提供信息，需要更好地理解环境线索和导致这种侵袭性表型的无数细胞类型之间的复杂相互作用。本综述重点关注肿瘤内血栓形成、缺氧和坏死的影响、适应性和先天免疫反应以及靶向治疗干预的现状。为了为未来的转化研究提供信息，需要更好地理解环境线索和导致这种侵袭性表型的无数细胞类型之间的复杂相互作用。本综述重点关注肿瘤内血栓形成、缺氧和坏死的影响、适应性和先天免疫反应以及靶向治疗干预的现状。