Glioblastoma Embryonic-like Stem Cells Exhibit Immune-Evasive Phenotype.

Publication Title

Cancers (Basel)

Authors

Borja Sesé
Sandra Íñiguez-Muñoz
Miquel Ensenyat-Mendez
Pere Llinàs-Arias
Guillem Ramis
Javier I Orozco, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, USAFollow
Silvia Fernández de Mattos
Priam Villalonga
Diego M Marzese

Document Type

Article

Publication Date

4-21-2022

Keywords

antigen presentation; epigenomics; glioblastoma; glioma stem cells; transcriptomics; california; sjci; psjhc

Abstract

BACKGROUND: Glioma stem cells (GSCs) have self-renewal and tumor-initiating capacities involved in drug resistance and immune evasion mechanisms in glioblastoma (GBM).

METHODS: Core-GSCs (c-GSCs) were identified by selecting cells co-expressing high levels of embryonic stem cell (ESC) markers from a single-cell RNA-seq patient-derived GBM dataset (

RESULTS: We identified a GSC population (4.22% ± 0.59) exhibiting concurrent high expression of ESC markers and downregulation of immune-associated pathways, named c-GSCs. In vitro ic-GSCs presented high expression of ESC markers and downregulation of antigen presentation HLA proteins. Transcriptomic analysis revealed a strong agreement of enriched biological pathways between tumor c-GSCs and in vitro ic-GSCs (

CONCLUSIONS: This study unravels glioblastoma immune-evasive mechanisms involving a c-GSC population. In addition, it provides a cellular model with paired gene expression, and DNA methylation maps to explore potential therapeutic complements for GBM immunotherapy.

Clinical Institute

Cancer

Specialty/Research Institute

Oncology