Disease-specific suppressive granulocytes participate in glioma progression
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....
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724013652 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jiarui Zhao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e4cb5418db7f407fa1440c88c5f4837f |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-e4cb5418db7f407fa1440c88c5f4837f2024-12-05T05:20:17ZengElsevierCell Reports2211-12472024-12-014312115014Disease-specific suppressive granulocytes participate in glioma progressionJiarui Zhao0Di Wu1Jiaqi Liu2Yang Zhang3Chunzhao Li4Weichen Zhao5Penghui Cao6Shixuan Wu7Mengyuan Li8Wenlong Li9Ying Liu10Yingying Huang11Ying Cao12Yiwen Sun13Ence Yang14Nan Ji15Jing Yang16Jian Chen17Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, ChinaBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, ChinaState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, ChinaDepartment 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, ChinaDepartment 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, ChinaChangping Laboratory, Beijing 102206, ChinaBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, ChinaBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, ChinaBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, ChinaBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, ChinaState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, ChinaState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, ChinaCenter for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, ChinaBeijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, ChinaDepartment of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment 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; Corresponding authorState 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; Corresponding authorBeijing 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724013652CP: Cancer |
| spellingShingle | 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 Disease-specific suppressive granulocytes participate in glioma progression Cell Reports CP: Cancer |
| title | Disease-specific suppressive granulocytes participate in glioma progression |
| title_full | Disease-specific suppressive granulocytes participate in glioma progression |
| title_fullStr | Disease-specific suppressive granulocytes participate in glioma progression |
| title_full_unstemmed | Disease-specific suppressive granulocytes participate in glioma progression |
| title_short | Disease-specific suppressive granulocytes participate in glioma progression |
| title_sort | disease specific suppressive granulocytes participate in glioma progression |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724013652 |
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