期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-28372-y
关键词
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资金
- NIH [1R01NS121405]
- Cancer Prevention & Research Institute of Texas [RP180882]
- Department of Defense [W81XWH-14-1-0115]
- Houston Methodist Foundation
- Donaldson Charitable Foundation
- Peak Foundation
- DOD Horizon Award [CA191052]
- University of Texas MD Anderson Moon Shots Program
- National Cancer Institute [P50CA127001]
- Broach Foundation for Brain Cancer Research
- Elias Family Fund
This study identifies molecular phenotypes of immune-suppressive and -promoting myeloid cells in GBM through single cell RNA sequencing and discovers S100A4 as a regulator of immune suppressive T and myeloid cells in GBM. The study reveals extensive spatial and molecular heterogeneity in immune infiltrates and identifies nine distinct myeloid cell subtypes, with five being prognostic indicators of glioma patient survival.
Glioblastoma (GBM) is an immune cold tumour that is refractory to immunotherapy. Here, the authors identify molecular phenotypes of immune-suppressive and -promoting myeloid cells in GBM through single cell RNA sequencing and propose S100A4 as a regulator of immune suppressive T and myeloid cells in GBM. A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates. We identify molecular signatures for nine distinct myeloid cell subtypes, of which five are independent prognostic indicators of glioma patient survival. Furthermore, we identify S100A4 as a regulator of immune suppressive T and myeloid cells in GBM and demonstrate that deleting S100a4 in non-cancer cells is sufficient to reprogram the immune landscape and significantly improve survival. This study provides insights into spatial, molecular, and functional heterogeneity of glioma and glioma-associated immune cells and demonstrates the utility of this dataset for discovering therapeutic targets for this poorly immunogenic cancer.
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