ABSTRACT
We leveraged IDH wild type glioblastomas (GBM) and derivative neurosphere models to define the tumor-intrinsic mRNA transcription phenotype. We found that intratumoral heterogeneity is reflected in the transcriptome and associated with increased tumor microenvironment presence. We performed in silico cell sorting to demonstrate that M2 macrophages/microglia are the most frequent type of immune cells in the glioma microenvironment, followed by CD4+ T lymphocytes. Longitudinal transcriptome analysis of 124 pairs of primary and recurrent glioma pairs showed expression subtype is retained in 53% of cases with no proneural to mesenchymal transition being apparent. Inference of the tumor microenvironment through gene signatures revealed a decrease in invading monocytes but a subtype dependent increase in M2 macrophages/microglia cells after disease recurrence. Our longitudinal expression dataset can be accessed at http://ackbar.cnio.es:3838/RecuR/. Our study provides a comprehensive transcriptional and cellular landscape of IDH wild type GBM during treatment modulated tumor evolution.
Footnotes
↵† Co-senior authors