The
tumor micro-environment (TME) plays an important role in various
cancers, including
gliomas. We estimated immune cell type-specific gene expression profiles in 3 large clinically annotated
glioma datasets using CIBERSORTx and LM22/
LM10 blood-based immune signatures and found that the proportions and estimated gene expression patterns of specific immune cells significantly varied according to IDH mutation status. When IDH-WT and IDH-MUT
tumors were considered separately, cluster-of-cluster analyses of immune cell gene expression identified groups with distinct survival outcomes. We confirmed and extended these findings by applying a signature matrix derived from single-cell
RNA-sequencing data derived from 19
glioma tumor samples to the bulk profiling data, validating findings from the LM22/
LM10 results. To link immune cell signatures with outcomes in checkpoint
therapy, we then showed a significant association of monocytic lineage cell gene expression clusters with patient survival and with mesenchymal gene expression scores. Integrating immune cell-based gene expression with previously described malignant cell states in
glioma demonstrated that macrophage M0 abundance significantly correlated with mesenchymal state in IDH-WT
gliomas, with evidence of a previously implicated role of the
Oncostatin-M receptor and macrophages in the mesenchymal state. Among IDH-WT
tumors that were enriched for the mesenchymal cell state, the estimated M0 macrophage expression signature coordinately also trended to a mesenchymal signature. We also examined IDH-MUT
tumors stratified by 1p/19q status, showing that a mesenchymal gene expression signature the M0 macrophage fraction was enriched in IDH-MUT, non-codeleted
tumors. Overall, these results highlight the
biological and clinical significance of the immune cell environment related to IDH mutation status, patient prognosis and the mesenchymal state in diffuse
gliomas.