Cellular characterization of the peritumoral brain zone of glioblastomas: heterogenous nature and clinical relevance
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Background
Glioblastoma (GB) is a highly aggressive cancer with nearly 100% recurrence, even after removal of all contrast-enhancing (CE) disease. This is primarily due to the persistence of residual tumor cells in the peritumoral brain zone (PBZ), which can repopulate the GB after treatment. The aim of this study was to characterize the degree of neoplastic infiltration and the tumor microenvironment (TME) in the periphery of these aggressive tumors.
Methods
We generated a prospective collection of radiologically guided biopsies from GB patients where we performed a comprehensive immunohistochemical analysis. We also integrated publicly available single-cell RNA sequencing datasets from human brains and gliomas to create an atlas of major cell types and select specific markers of immune cells, astrocytes, oligodendrocytes, and vascular cells. This gene panel was used to characterize the cellular content of biopsies from various regions, including CE tumor, non-CE tumor, edema, and radiologically normal tissue.
Results
High levels of GB infiltration were found in non-CE regions, which explains the clinical benefit of extending surgery to these areas. However, tumorigenic signs were also found in areas that were associated with vasculogenic edema. The analysis of the biopsies revealed inter-tumor heterogeneity in the PBZ, with variations in cellular composition linked to tumor infiltration, patient age, and sex. Additionally, we identified cellular features, both in the tumor core and the periphery, that were distinctly associated with the prognosis of the patients depending on the extent of resection.
Conclusions
Our results support the notion that non-CE tumor areas are infiltrated by GB cells, although they expand as well to extra-tumoral regions. Moreover, our characterization of the cellular profile of the PBZ suggest key targets for GB progression, which might be different in patients receiving complete or uncomplete resections of the CE disease, or in female vs male patients.
