Current Knowledge about the Peritumoral Microenvironment in Glioblastoma

Abstract

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.

Unveiling novel cell clusters and biomarkers in glioblastoma and its peritumoral microenvironment at the single-cell perspective

“…PBZ is more like a transitional zone with a precancerous microenvironment, which is the basis for glioblastoma progression and recurrence. The understanding of PBZ may be related to the development of more effective treatment methods to prevent the development and recurrence of glioblastoma [ 13 ].…”

Progress in Glioma Stem Cell Research

“…Multiple mechanisms are involved in the chemoresistance of GBM, that is, overexpression of drug efflux transporter pumps such as P-glycoprotein, cancer stem cells, augmented DNA repair mechanisms, and dysregulation of apoptosis; this is considered to be an important factor responsible for drug resistance in GBM [ 19 ]. These factors highly influence the remarkable changes in tumor cells that lead to chemoresistance, but recently, new evidence has shown that the tumor microenvironment also plays a key role in chemosensitivity [ 20 , 21 ]. In addition to tumor cells, tumor lesions also contain a variety of stromal cells, including inflammatory blood cells, which infiltrate tumors, and endothelial cells (EC), which form blood vessels [ 22 ].…”