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
Affiliations
Jiarui Zhao
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
Di Wu
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
Jiaqi Liu
State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China
Yang Zhang
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
Chunzhao Li
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
Weichen Zhao
Changping Laboratory, Beijing 102206, China
Penghui Cao
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
Shixuan Wu
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
Mengyuan Li
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
Wenlong Li
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
Ying Liu
State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China
Yingying Huang
State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China
Ying Cao
Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
Yiwen Sun
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
Ence Yang
Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Nan Ji
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; Corresponding author
Jing Yang
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; Corresponding author
Jian Chen
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; Corresponding author
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.
