Nusraty Sabrina, Boddeti Ujwal, Zaghloul Kareem A, Brown Desmond A
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Cancers (Basel). 2024 May 22;16(11):1972. doi: 10.3390/cancers16111972.
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.
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，诊断后的中位生存期为15个月。尽管常规治疗方案包括最大程度的安全神经外科切除，随后进行辅助放疗和化疗，但该疾病仍然无一例外是致命的。与GBM相关的预后不良是多因素导致的，这是由于增殖增加、血管生成以及代谢转换为糖酵解途径等因素。至关重要的是，GBM介导的局部和全身免疫抑制导致免疫监视不足，最终导致肿瘤免疫逃逸。小胶质细胞——中枢神经系统（CNS）的常驻巨噬细胞——在介导大脑局部免疫反应中起关键作用。根据特定的病理线索，小胶质细胞被激活为促炎、神经毒性表型，即M1型，或抗炎、再生表型，即M2型。在任何一种情况下，小胶质细胞都会分泌相应的促炎或抗炎细胞因子和趋化因子，这些因子要么促进要么阻碍肿瘤生长。在此，我们综述了GBM细胞与常驻小胶质细胞之间的相互作用，重点关注当代研究，这些研究突出了GBM对所表达的小胶质细胞亚型、分泌的相关细胞因子/趋化因子的影响，以及最终它们对肿瘤发病机制的影响。最后，我们探讨了理解肿瘤免疫格局的复杂性如何为针对这种毁灭性疾病的新型免疫治疗策略提供信息。
