IMPS-16MESENCHYMAL TYPE GLIOMA STEM CELL EXPRESS ICOS LIGAND AND UPREGULATE ICOS+IL-10+T CELLS

Abstract

Tumor heterogeneity of high-grade glioma (HGG) is recognized by four clinically relevant subtypes based on core gene signatures. Glioma stem cells, which is isolated from patient-derived glioma sphere cultures, also resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. The aims of this study were the immunobiological characterization of MES and PN GSCs. GSCs were generated and examined by microarray, and flow cytometry for expression of B7 family. The B7 family ligands and their receptors play a critical role in activation, expansion, as well as contraction of T cell populations. Only MES GSCs express Inducible Co-stimulatory Ligand (ICOSLG). In vitro analysis, we found MES GSC have the potential to prime CD4+ T-cells to differentiate into IL-10-producing T regulatory cells through ICOSLG. Moreover, we found that a subset of the PN GSCs undergoes differentiation to a MES state in a TNF-alfa-dependent manner with an associated upregulation of CD44 and ICOSLG. We further show that the MES signature, CD44 expression, and ICOSLG expression correlate with shorter survival in patients with GBM.