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Disease-specific suppressive granulocytes participate in glioma progression

Authors :
Jiarui Zhao
Di Wu
Jiaqi Liu
Yang Zhang
Chunzhao Li
Weichen Zhao
Penghui Cao
Shixuan Wu
Mengyuan Li
Wenlong Li
Ying Liu
Yingying Huang
Ying Cao
Yiwen Sun
Ence Yang
Nan Ji
Jing Yang
Jian Chen
Source :
Cell Reports, Vol 43, Iss 12, Pp 115014- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: Glioblastoma represents one of the most aggressive cancers, characterized by severely limited therapeutic options. Despite extensive investigations into this brain malignancy, cellular and molecular components governing its immunosuppressive microenvironment remain incompletely understood. Here, we identify a distinct neutrophil subpopulation, termed disease-specific suppressive granulocytes (DSSGs), present in human glioblastoma and lower-grade gliomas. DSSGs exhibit the concurrent expression of multiple immunosuppressive and immunomodulatory signals, and their abundance strongly correlates with glioma grades and poor clinical outcomes. Genetic disruption of neutrophil recruitment in immunocompetent mouse models of gliomas, achieved through Cxcl1 knockout in glioma cells or host-specific Cxcr2 deletion or diphtheria toxin A-mediated neutrophil depletion, can significantly enhance antitumor immunity and prolong survival. Further, we reveal that the skull bone marrow and meninges can be the primary sources of neutrophils and DSSGs in human and mouse glioma tumors. These findings demonstrate a critical mechanism underlying the establishment of the immunosuppressive microenvironment in gliomas.

Details

Language :
English
ISSN :
22111247
Volume :
43
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.4cb5418db7f407fa1440c88c5f4837f
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2024.115014