文章：

胶质母细胞瘤中的小胶质细胞：分子机制与免疫治疗潜力

Microglia in Glioblastomas: Molecular Insight and Immunotherapeutic Potential

原文发布日期：22 May 2024

DOI: 10.3390/cancers16111972

类型: Article

开放获取: 是

英文摘要：

Glioblastoma (GBM) is one of the most aggressive and devastating primary brain tumors, with a median survival of 15 months following diagnosis. Despite the intense treatment regimen which routinely includes maximal safe neurosurgical resection followed by adjuvant radio- and chemotherapy, the disease remains uniformly fatal. The poor prognosis associated with GBM is multifactorial owing to factors such as increased proliferation, angiogenesis, and metabolic switching to glycolytic pathways. Critically, GBM-mediated local and systemic immunosuppression result in inadequate immune surveillance and ultimately, tumor-immune escape. Microglia—the resident macrophages of the central nervous system (CNS)—play crucial roles in mediating the local immune response in the brain. Depending on the specific pathological cues, microglia are activated into either a pro-inflammatory, neurotoxic phenotype, known as M1, or an anti-inflammatory, regenerative phenotype, known as M2. In either case, microglia secrete corresponding pro- or anti-inflammatory cytokines and chemokines that either promote or hinder tumor growth. Herein, we review the interplay between GBM cells and resident microglia with a focus on contemporary studies highlighting the effect of GBM on the subtypes of microglia expressed, the associated cytokines/chemokines secreted, and ultimately, their impact on tumor pathogenesis. Finally, we explore how understanding the intricacies of the tumor-immune landscape can inform novel immunotherapeutic strategies against this devastating disease.

摘要翻译： 

胶质母细胞瘤（GBM）是最具侵袭性和破坏性的原发性脑肿瘤之一，确诊后中位生存期仅为15个月。尽管常规采用最大范围安全神经外科切除联合辅助放化疗的强化治疗方案，该疾病仍具有普遍致死性。GBM预后不良是多因素作用的结果，包括肿瘤增殖增强、血管生成以及代谢向糖酵解途径转换等。关键在于，GBM介导的局部和全身免疫抑制导致免疫监视功能不足，最终引发肿瘤免疫逃逸。小胶质细胞作为中枢神经系统的常驻巨噬细胞，在介导脑部局部免疫反应中发挥关键作用。根据特定病理信号，小胶质细胞可被激活为促炎性神经毒性表型（M1型）或抗炎性再生表型（M2型）。两种表型均会分泌相应的促炎或抗炎细胞因子及趋化因子，从而促进或抑制肿瘤生长。本文系统综述了GBM细胞与常驻小胶质细胞间的相互作用机制，重点聚焦当代研究揭示的GBM对小胶质细胞亚型表达的影响、相关细胞因子/趋化因子的分泌特征，及其最终对肿瘤发病机制的影响。最后，我们探讨了如何通过解析肿瘤免疫微环境的复杂网络，为开发针对这一致命疾病的新型免疫治疗策略提供理论依据。

原文链接：

Microglia in Glioblastomas: Molecular Insight and Immunotherapeutic Potential