Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression

被引：173

作者：

Yeo, Alan T. ^{[1
,2
]}

Rawal, Shruti ^{[1
]}

Delcuze, Bethany ^{[1
,2
]}

Christofides, Anthos ^{[1
]}

Atayde, Agata ^{[1
]}

Strauss, Laura ^{[1
]}

Balaj, Leonora ^{[3
]}

Rogers, Vaughn A. ^{[1
]}

Uhlmann, Erik J. ^{[4
]}

Varma, Hemant ^{[5
]}

Carter, Bob S. ^{[3
]}

Boussiotis, Vassiliki A. ^{[1
,6
]}

Charest, Al ^{[1
,6
]}

机构：

[1] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA

[2] Tufts Univ, Sch Med, Sackler Sch Grad Studies, Boston, MA 02111 USA

[3] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA

[4] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA

[5] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA

[6] Beth Israel Deaconess Med Ctr, Canc Res Inst, Boston, MA 02215 USA

来源：

NATURE IMMUNOLOGY | 2022年 / 23卷 / 06期

基金：

美国国家卫生研究院;

关键词：

PERIVASCULAR MACROPHAGES; SUPPRESSOR-CELLS; CROSS-TALK; EXPRESSION; MOUSE; RECEPTOR; IMMUNOTHERAPY; PROLIFERATION; ANGIOGENESIS; TEMOZOLOMIDE;

D O I：

10.1038/s41590-022-01215-0

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. Single-cell RNAseq during initiation and progression of mouse glioblastoma reveals a dynamic immune microenvironment transitioning from pro-inflammatory microglia in early tumors towards an infiltrating macrophage and suppressor cell-centric immune landscape in late-stage tumors.

引用

页码：971 / +

页数：38

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