Figure 4. IDH mutation status shapes TAM activation in gliomas.
(A) Number of MG and MDM per mm2 inside the perivascular niche (PVN) or distant from the PVN (non-PVN) within IDH wt gliomas by IF staining. Means compared with Wilcoxon signed-rank test: ***p < 0.001. (B) Distance of MG and MDM to nearest vessel in IDH wt gliomas (nsamples=14, nMG=88781 and nMDM=92969 cells counted). (C) Box plot of HLA-DR geometric mean fluorescence intensity measured by FCM in MG and MDM in IDH mut and IDH wt gliomas. MG and MDM from the same samples are connected by lines (nIDHmut=17, nIDHwt=39, Wilcoxon signed-rank test: ***p < 0.001, ****p < 0.0001). (D) GSVA of antigen-processing and -presentation pathways from Molecular Signatures Database (MSigDB) “Canonical Pathways” collection with significant differential enrichment between MG and MDM in IDH wt tumors, and in MG and MDM across IDH mut and IDH wt samples. Columns ordered by IDH mutation status and cell type, rows (z-score) hierarchically clustered. (E) Expression heatmap of T-MG and (F) T-MDM DEGs (compared to T-MG in IDH mut gliomas) in IDH mut and IDH wt glioma samples. Columns and rows (z-score) hierarchically clustered. (G) Normalized counts of selected genes in MG and MDM in gliomas stratified by IDH status. (H) Relative expression in CD45−, MG and MDM cells of ligands and receptors upregulated in CD45− cells in IDH wt vs. IDH mut samples and their matching counterparts. Variance-stabilized expression values were scaled to the expression range. (I) Kaplan-Meier estimator of survival in TCGA glioma cohort based on enrichment for MDM IDH wt signature assessed by GSVA in IDH mut and IDH wt gliomas from combined TCGA cohort. GSVA scores were separated into tertiles across combined IDH mut and IDH wt sample set. Pairwise p values calculated using log-rank test. (J) Hazard ratios of multivariate cox proportional hazards model with transcriptomic subtype (TCGA annotation), IDH status (TCGA annotation) and T-MDM IDH wt GSVA score as covariates for overall survival within TCGA glioma cohort (PN = proneural, NE = neural, CL = classical, and ME = mesenchymal subtype).