Disease-specific suppressive granulocytes participate in glioma progression

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

doi:10.1016/j.celrep.2024.115014

Disease-specific suppressive granulocytes participate in glioma progression

Cell Rep. 2024 Dec 3;43(12):115014. doi: 10.1016/j.celrep.2024.115014. Online ahead of print.

Authors

Jiarui Zhao¹, Di Wu¹, Jiaqi Liu², Yang Zhang³, Chunzhao Li³, Weichen Zhao⁴, Penghui Cao¹, Shixuan Wu¹, Mengyuan Li¹, Wenlong Li¹, Ying Liu², Yingying Huang², Ying Cao⁵, Yiwen Sun¹, Ence Yang⁶, Nan Ji⁷, Jing Yang⁸, Jian Chen⁹

Affiliations

¹ Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, China.
² State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China.
³ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
⁴ Changping Laboratory, Beijing 102206, China.
⁵ Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
⁶ Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
⁷ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China. Electronic address: jinan@bjtth.org.
⁸ State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; Peking University Third Hospital Cancer Center, Beijing 100191, China. Electronic address: jing.yang@pku.edu.cn.
⁹ Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, China; Changping Laboratory, Beijing 102206, China. Electronic address: chenjian@cibr.ac.cn.

PMID: 39630582
DOI: 10.1016/j.celrep.2024.115014

Abstract

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.

Keywords: CP: Cancer.