Glioblastoma is a deadly disease, with a mean overall survival of less than 2 years from diagnosis. Recurrence after gross total surgical resection and adjuvant chemo-radiotherapy almost invariably occurs within the so-called peritumoral brain zone (PBZ). The aim of this narrative review is to summarize the most relevant findings about the biological characteristics of the PBZ currently available in the medical literature. The PBZ presents several peculiar biological characteristics. The cellular landscape of this area is different from that of healthy brain tissue and is characterized by a mixture of cell types, including tumor cells (seen in about 30% of cases), angiogenesis-related endothelial cells, reactive astrocytes, glioma-associated microglia/macrophages (GAMs) with anti-inflammatory polarization, tumor-infiltrating lymphocytes (TILs) with an “exhausted” phenotype, and glioma-associated stromal cells (GASCs). From a genomic and transcriptomic point of view, compared with the tumor core and healthy brain tissue, the PBZ presents a “half-way” pattern with upregulation of genes related to angiogenesis, the extracellular matrix, and cellular senescence and with stemness features and downregulation in tumor suppressor genes. This review illustrates that the PBZ is a transition zone with a pre-malignant microenvironment that constitutes the base for GBM progression/recurrence. Understanding of the PBZ could be relevant to developing more effective treatments to prevent GBM development and recurrence.
胶质母细胞瘤是一种致命性疾病，自确诊起平均总生存期不足两年。在肉眼全切手术及辅助放化疗后，复发几乎总是发生在所谓的瘤周脑区。本叙述性综述旨在总结目前医学文献中关于瘤周脑区生物学特征的最重要发现。该区域具有若干独特的生物学特性：其细胞构成与健康脑组织存在差异，呈现多种细胞类型混合的特征，包括肿瘤细胞（约占30%病例）、血管生成相关内皮细胞、反应性星形胶质细胞、具有抗炎极化的胶质瘤相关小胶质细胞/巨噬细胞、呈现“耗竭”表型的肿瘤浸润淋巴细胞以及胶质瘤相关基质细胞。从基因组和转录组学角度看，与肿瘤核心区和健康脑组织相比，瘤周脑区呈现“中间态”特征——血管生成相关基因、细胞外基质相关基因、细胞衰老相关基因表达上调并具有干细胞特性，同时肿瘤抑制基因表达下调。本综述阐明瘤周脑区是具有癌前微环境的过渡区域，为胶质母细胞瘤进展/复发提供了基础。深入理解瘤周脑区特征对于开发更有效的治疗方案以预防胶质母细胞瘤发生及复发具有重要意义。
Current Knowledge about the Peritumoral Microenvironment in Glioblastoma
肿瘤(癌症)患者之家