Current Knowledge about the Peritumoral Microenvironment in Glioblastoma

Area of Science:

• Neuro-oncology
• Cancer Biology
• Genomics

Background:

• Glioblastoma (GBM) is a fatal brain cancer with poor survival rates.
• Tumor recurrence often originates in the peritumoral brain zone (PBZ) after initial treatment.
• The PBZ's biological characteristics are critical for understanding GBM progression.

Purpose of the Study:

• To review current medical literature on the biological features of the PBZ.
• To elucidate the cellular and molecular landscape of the PBZ in GBM.
• To highlight the PBZ's role in GBM recurrence and treatment resistance.

Main Methods:

• Narrative review of existing scientific literature.
• Analysis of cellular composition within the PBZ.
• Examination of genomic and transcriptomic alterations in the PBZ.

Main Results:

• The PBZ contains diverse cells including tumor cells, endothelial cells, astrocytes, microglia/macrophages (GAMs), lymphocytes (TILs), and stromal cells (GASCs).
• Genomic and transcriptomic analysis reveals a distinct 'half-way' pattern in the PBZ, with upregulated angiogenesis, extracellular matrix, senescence, and stemness genes.
• Downregulation of tumor suppressor genes is also observed in the PBZ.
• GAMs exhibit anti-inflammatory polarization, and TILs show an 'exhausted' phenotype.

Conclusions:

• The PBZ is a pre-malignant microenvironment facilitating GBM growth and recurrence.
• Its unique cellular and molecular profile makes it a critical target for novel therapeutic strategies.
• Further understanding of the PBZ is essential for improving GBM treatment outcomes and preventing relapse.