神经胶质瘤是一组不同的原发性中枢神经系统肿瘤，目前尚无有效的治疗方法。脑巨噬细胞包括脑实质中的小胶质细胞、脑膜-脉络丛-血管周围空间中的边界相关巨噬细胞以及浸润大脑的单核细胞衍生的巨噬细胞。随着我们对脑巨噬细胞认识的极大提高，在神经胶质瘤中发现了不同的巨噬细胞群，它们表现出功能和表型异质性。长期以来，我们一直认为脑巨噬细胞衰老是有害的，表现为特殊形式的持续细胞周期停滞和慢性低度炎症。巨噬细胞的持续衰老可能导致免疫功能障碍，可能导致神经胶质瘤的发生和发展。鉴于脑巨噬细胞在神经胶质瘤中发挥的关键作用，我们揭示了脑巨噬细胞如何进行重编程及其对神经胶质瘤的贡献。我们概述了衰老脑巨噬细胞的一般分子改变和特定生物标志物，以及功能变化（如代谢、自噬、吞噬作用、抗原呈递、浸润和募集）。此外，还讨论了与衰老脑巨噬细胞相关的遗传调控和机制的最新进展。特别是，这篇综述强调了衰老脑巨噬细胞对神经胶质瘤的贡献，这可能会推动利用脑巨噬细胞作为神经胶质瘤的预后标志物或/和治疗目标的转化努力。深入理解脑巨噬细胞衰老如何在功能上影响肿瘤微环境将是我们开发神经胶质瘤创新疗法的关键。版权所有 © 2024 Elsevier Ltd. 保留所有权利。

Gliomas are a diverse group of primary central nervous system neoplasms with no curative therapies available. Brain macrophages comprise microglia in the brain parenchyma, border-associated macrophages in the meningeal-choroid plexus-perivascular space and monocyte-derived macrophages infiltrating the brain. With the great improvement of our recognition of brain macrophages, diverse macrophage populations have been found in the context of glioma, which exhibit functional and phenotypic heterogeneity. We have long thought that brain macrophage senescence is detrimental, manifested by specialized forms of persistent cell cycle arrest and chronic low-grade inflammation. Persistent senescence of macrophages may result in immune dysfunction, potentially contributing to glioma initiation and development. Given the crucial roles played by brain macrophages in glioma, we unravel how brain macrophages undergo reprogramming and their contribution to glioma. We outline general molecular alterations and specific biomarkers in senescent brain macrophages, as well as functional changes (such as metabolism, autophagy, phagocytosis, antigen presentation, and infiltration and recruitment). In addition, recent advances in genetic regulation and mechanisms linked to senescent brain macrophages are discussed. In particular, this review emphasizes the contribution of senescent brain macrophages to glioma, which may drive translational efforts to utilize brain macrophages as a prognostic marker or/and treatment target in glioma. An in-depth comprehending of how brain macrophage senescence functionally influences the tumor microenvironment will be key to our development of innovative therapeutics for glioma.Copyright © 2024 Elsevier Ltd. All rights reserved.