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Single-cell RNA sequencing reveals immunosuppressive myeloid cell diversity during malignant progression in a murine model of glioma.
Rajendran, Sakthi; Hu, Yang; Canella, Alessandro; Peterson, Clayton; Gross, Amy; Cam, Maren; Nazzaro, Matthew; Haffey, Abigail; Serin-Harmanci, Akdes; Distefano, Rosario; Nigita, Giovanni; Wang, Wesley; Kreatsoulas, Daniel; Li, Zihai; Sepeda, Jesse A; Sas, Andrew; Hester, Mark E; Miller, Katherine E; Elemento, Olivier; Roberts, Ryan D; Holland, Eric C; Rao, Ganesh; Mardis, Elaine R; Rajappa, Prajwal.
Afiliação
  • Rajendran S; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Hu Y; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
  • Canella A; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Peterson C; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Gross A; Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
  • Cam M; Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
  • Nazzaro M; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Haffey A; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Serin-Harmanci A; Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
  • Distefano R; Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • Nigita G; Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • Wang W; Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • Kreatsoulas D; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • Li Z; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • Sepeda JA; Department of Neurology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Neuroscience Research Institute, The Ohio State University, Columbus, OH, USA.
  • Sas A; Department of Neurology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Neuroscience Research Institute, The Ohio State University, Columbus, OH, USA.
  • Hester ME; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Neurology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Pediatrics, The Ohio State University Wexner Medical Center
  • Miller KE; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Elemento O; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
  • Roberts RD; Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
  • Holland EC; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Rao G; Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
  • Mardis ER; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus
  • Rajappa P; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus
Cell Rep ; 42(3): 112197, 2023 03 28.
Article em En | MEDLINE | ID: mdl-36871221
ABSTRACT
Recent studies have shown the importance of the dynamic tumor microenvironment (TME) in high-grade gliomas (HGGs). In particular, myeloid cells are known to mediate immunosuppression in glioma; however, it is still unclear if myeloid cells play a role in low-grade glioma (LGG) malignant progression. Here, we investigate the cellular heterogeneity of the TME using single-cell RNA sequencing in a murine glioma model that recapitulates the malignant progression of LGG to HGG. LGGs show increased infiltrating CD4+ and CD8+ T cells and natural killer (NK) cells in the TME, whereas HGGs abrogate this infiltration. Our study identifies distinct macrophage clusters in the TME that show an immune-activated phenotype in LGG but then evolve to an immunosuppressive state in HGG. We identify CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Targeting these intra-tumoral macrophages in the LGG stage may attenuate their immunosuppressive properties and impair malignant progression.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioma Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioma Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos