First Author | Yeo AT | Year | 2022 |
Journal | Nat Immunol | Volume | 23 |
Issue | 6 | Pages | 971-984 |
PubMed ID | 35624211 | Mgi Jnum | J:330339 |
Mgi Id | MGI:7377821 | Doi | 10.1038/s41590-022-01215-0 |
Citation | Yeo AT, et al. (2022) Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression. Nat Immunol 23(6):971-984 |
abstractText | 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(+) CD8(+)T 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. |