School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, and.
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
J Clin Invest. 2023 Jan 3;133(1):e163451. doi: 10.1172/JCI163451.
Glioblastoma (GBM) is the most belligerent and frequent brain tumor in adults. Research over the past two decades has provided increased knowledge of the genomic and molecular landscape of GBM and highlighted the presence of a high degree of inter- and intratumor heterogeneity within the neoplastic compartment. It is now appreciated that GBMs are composed of multiple distinct and impressionable neoplastic and non-neoplastic cell types that form the unique brain tumor microenvironment (TME). Non-neoplastic cells in the TME form reciprocal interactions with neoplastic cells to promote tumor growth and invasion, and together they influence the tumor response to standard-of-care therapies as well as emerging immunotherapies. One of the most prevalent non-neoplastic cell types in the GBM TME are myeloid cells, the most abundant of which are of hematopoietic origin, including monocytes/monocyte-derived macrophages. Less abundant, although still a notable presence, are neutrophils of hematopoietic origin and intrinsic brain-resident microglia. In this Review we focus on neutrophils and monocytes that infiltrate tumors from the blood circulation, their heterogeneity, and their interactions with neoplastic cells and other non-neoplastic cells in the TME. We conclude with an overview of challenges in targeting these cells and discuss avenues for therapeutic exploitation to improve the dismal outcomes of patients with GBM.
胶质母细胞瘤（GBM）是成人中最具侵袭性和最常见的脑肿瘤。过去二十年的研究提供了对 GBM 基因组和分子特征的更多了解，并强调了肿瘤区内存在高度的肿瘤内和肿瘤间异质性。现在人们认识到，GBM 由多种不同的、有影响力的肿瘤性和非肿瘤性细胞类型组成，这些细胞形成独特的脑肿瘤微环境（TME）。TME 中的非肿瘤细胞与肿瘤细胞形成相互作用，促进肿瘤生长和侵袭，它们共同影响肿瘤对标准治疗方法以及新兴免疫疗法的反应。在 GBM TME 中最常见的非肿瘤细胞类型之一是髓样细胞，其中最丰富的是造血来源的单核细胞/单核细胞衍生的巨噬细胞。数量较少，但仍然存在的是造血来源的中性粒细胞和固有脑驻留的小胶质细胞。在这篇综述中，我们重点介绍从血液循环中浸润肿瘤的中性粒细胞和单核细胞、它们的异质性以及它们与 TME 中的肿瘤细胞和其他非肿瘤细胞的相互作用。最后，我们概述了针对这些细胞的挑战，并讨论了利用这些细胞进行治疗的途径，以改善 GBM 患者的悲惨结局。
