Table 1.

GBM molecular classification and associated immune phenotypes.

Classifier		Neural	Proneural	Classical	Mesenchymal
Geneticsa		Expression of neuron markers such as NEFL, GABRA1, SYT1 and SLC12A5 Association with GO categories linked to the neuron projection and axon and synaptic transmission	PDGFRA mutations, especially in the Ig-domain Point mutation in IDH1 associated with higher CpG island methylation Focal amplification of the locus at 4q12 harboring PDGFRA High level of PDGFRA expression TP53 mutation Loss of heterozygosity Chromosome 7 amplification paired to loss of chromosome 10 only in 50% of the cases High expression of oligodendrocytic development genes Expression of proneural development genes	Chromosome 7 amplification paired with chromosome 10 loss High level of EGFR amplification High level of EGFR alterations Lack of TP53 mutations Focal 9p21.3 homozygous deletion, targeting CDKN2A High expression of neural precursors and stem cell markers	Focal hemizygous deletion of a region at 17q11.2 Low expression of NF1 Co-mutations of NF1 and PTEN Expression of mesenchymal markers (CHI3L1, CD44, MERKT, YKL40 and MET) High expression of genes implicated in the NFKB and tumor necrosis factor super family pathways (TRADD, RELB, TNFRSF1A) High expression of microglial markers such as CD68 and PTPRC
Immune cell Infiltratesb	Tumor core	Macrophages (CD163)	Macrophages (CD163)	Macrophages (CD163) +	Macrophages (CD163) +++
	Tumor edge	Microglia (CD68) ++	Microglia (CD68)	Microglia (CD68) +	Microglia (CD68) +++
	Perivascular area	CD4 T cells ++ CD8 T cells	CD4 T cells CD8 T cells	CD4 T cells + CD8 T cells	CD4 T cells +++ CD8 T cells
Immune markersc, d		PD-1	PD-1	IL-12, PD-1	Galectin 3, IL-10, IL-23, TGFβ, PD-L1, CD163, CCR2, CCL-22, CD47, CSF-1, MIC-1, IL-6, CTLA-4, Arginase, CD204, IL1, IL-15, IL-7, CD278, IDO
Re-classificatione		≪ Healthy brain ≫	Combination of OPC-and NPC-like	AC-like	MES-like
Associated gene mutation with the re-classification e			PDGFRA and CDK4 mutations, respectively	EGFR mutation	NF1 mutation

^aVerhaak RG et al. (19). Cancer Cell 17: 98-110.

^bMartinez-Lage M et al. (28). Acta Neuropathol Commun 7: 203.

^cDoucette T et al. (29). Cancer Immunol Res 1: 112-122.

^dWang Q et al. (20). Cancer Cell 32: 42-56.

^eNeftel C et al. (4). Cell 178:835-849.