Single-cell RNA Sequencing Reveals Evolution of Immune Landscape During Glioblastoma Progression

Overview

Journal Nat Immunol

Date 2022 May 27

PMID 35624211

Authors

Alan T Yeo

Shruti Rawal

Bethany Delcuze

Anthos Christofides

Agata Atayde

Laura Strauss

Leonora Balaj

Vaughn A Rogers

Erik J Uhlmann

Hemant Varma

Bob S Carter

Vassiliki A Boussiotis

Al Charest

Affiliations

Soon will be listed here.

Abstract

Glioblastoma (GBM) is an incurable primary malignant brain cancer hallmarked with a substantial protumorigenic immune component. Knowledge of the GBM immune microenvironment during tumor evolution and standard of care treatments is limited. Using single-cell transcriptomics and flow cytometry, we unveiled large-scale comprehensive longitudinal changes in immune cell composition throughout tumor progression in an epidermal growth factor receptor-driven genetic mouse GBM model. We identified subsets of proinflammatory microglia in developing GBMs and anti-inflammatory macrophages and protumorigenic myeloid-derived suppressors cells in end-stage tumors, an evolution that parallels breakdown of the blood-brain barrier and extensive growth of epidermal growth factor receptor GBM cells. A similar relationship was found between microglia and macrophages in patient biopsies of low-grade glioma and GBM. Temozolomide decreased the accumulation of myeloid-derived suppressor cells, whereas concomitant temozolomide irradiation increased intratumoral GranzymeB CD8T cells but also increased CD4 regulatory T cells. These results provide a comprehensive and unbiased immune cellular landscape and its evolutionary changes during GBM progression.

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