Silver Aryeh, Feier Diana, Ghosh Tanya, Rahman Maryam, Huang Jianping, Sarkisian Matthew R, Deleyrolle Loic P
Department of Neurosurgery, Adam Michael Rosen Neuro-Oncology Laboratories, University of Florida, Gainesville, FL, United States.
Preston A. Wells, Jr. Center for Brain Tumor Therapy, University of Florida, Gainesville, FL, United States.
Front Oncol. 2022 Oct 19;12:1022716. doi: 10.3389/fonc.2022.1022716. eCollection 2022.
Glioblastoma (GBM) is an extremely aggressive and incurable primary brain tumor with a 10-year survival of just 0.71%. Cancer stem cells (CSCs) are thought to seed GBM's inevitable recurrence by evading standard of care treatment, which combines surgical resection, radiotherapy, and chemotherapy, contributing to this grim prognosis. Effective targeting of CSCs could result in insights into GBM treatment resistance and development of novel treatment paradigms. There is a major ongoing effort to characterize CSCs, understand their interactions with the tumor microenvironment, and identify ways to eliminate them. This review discusses the diversity of CSC lineages present in GBM and how this glioma stem cell (GSC) mosaicism drives global intratumoral heterogeneity constituted by complex and spatially distinct local microenvironments. We review how a tumor's diverse CSC populations orchestrate and interact with the environment, especially the immune landscape. We also discuss how to map this intricate GBM ecosystem through the lens of metabolism and immunology to find vulnerabilities and new ways to disrupt the equilibrium of the system to achieve improved disease outcome.
胶质母细胞瘤（GBM）是一种极具侵袭性且无法治愈的原发性脑肿瘤，其10年生存率仅为0.71%。癌症干细胞（CSC）被认为是导致GBM不可避免复发的根源，因为它们能够逃避包括手术切除、放疗和化疗在内的标准治疗，从而导致了这种严峻的预后情况。有效靶向癌症干细胞可能会为了解GBM治疗耐药性以及开发新的治疗模式带来启示。目前正在进行一项重大努力，旨在对癌症干细胞进行表征，了解它们与肿瘤微环境的相互作用，并确定消除它们的方法。本综述讨论了GBM中存在的癌症干细胞谱系的多样性，以及这种胶质瘤干细胞（GSC）嵌合现象如何驱动由复杂且空间上不同的局部微环境构成的肿瘤内整体异质性。我们回顾了肿瘤中不同的癌症干细胞群体如何与环境相互协调和相互作用，尤其是与免疫环境的相互作用。我们还讨论了如何从代谢和免疫学的角度绘制这个复杂的GBM生态系统，以找到其脆弱性以及破坏系统平衡以改善疾病预后的新方法。
