Tmic-17. subtype-specific cellular composition of the glioblastoma microenvironment

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor, which has a dismal prognosis in spite of an aggressive, multi-modal treatment regimen. The Cancer Genome Atlas has identified four major subtypes based on distinct genetic signatures. These subtypes are referred to as proneural, neural, mesenchymal, and classical based on their associations with diverse neural cell lineages. The mesenchymal subtype, for example, shows enrichment of immune response-related genes and an association with tumor-associated macrophages (TAMs). TAMs have been shown to promote GBM growth and progression and, along with other non-neoplastic cells, they constitute integral elements of the GBM microenvironment. In light of the molecular heterogeneity among the distinct subgroups, we postulated corresponding subtype-specific differences in the cellular composition of the associated microenvironment. In order to test this hypothesis, immunohistochemical analysis of the proneural, classical, and mesenchymal subtypes was performed in order to identify various non-neoplastic cell populations and their relative abundance. Human data were validated using genetically engineered mouse models of proneural and mesenchymal GBM. Quantification of immunohistochemical staining for distinct markers revealed an increased infiltration of immune cells, including TAMs and CD8-positive T cells, in the mesenchymal subtype in both human and mouse. Furthermore, TAM-positive area positively corr...

Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kaffes, I., Szulzewsky, F., Alikhanyan, K., Herting, C., Shelton, J., Uhrbom, L., Nilsson, K. F., Nelander, S., Westermark, B., Huse, J., Holland, E., Brat, D., Hambardzumyan, D. Tags: TUMOR MICROENVIRONMENT Source Type: research