Immune cell gene expression signatures in diffuse glioma are associated with IDH mutation status, patient outcome and malignant cell state, and highlight the importance of specific cell subsets in glioma biology

Abstract

This presentation will discuss the biological and clinical significance of the immune cell environment related to IDH mutation status, patient prognosis and the mesenchymal state in diffuse gliomas. The tumor micro-environment (TME) plays critical role in various cancers, including gliomas. We estimated immune cell type-specific gene expression profiles in glioma datasets and found estimated proportions and gene expression profiles that varied according to IDH mutation status. Cluster-of-cluster analyses of immune cell gene expression identified groups with distinct survival outcomes in IDH-WT and IDH-MUT tumors. We verified these findings by applying a signature matrix derived from single-cell RNA Seq data. To link immune cell signatures with outcomes in checkpoint therapy, we found a significant association of monocytic gene expression clusters with patient survival and with mesenchymal scores. Integrating immune cell-based gene expressions with previously described malignant cell states in glioma demonstrated that macrophage M0 abundance significantly correlated with mesenchymal state in IDH-WT gliomas. Overall, these results highlight biological and clinical significance of immune cell environment related to IDH mutation status, patient prognosis and the mesenchymal state in diffuse gliomas.