Cell Reports (Mar 2023)
Single-cell RNA sequencing reveals immunosuppressive myeloid cell diversity during malignant progression in a murine model of glioma
- Sakthi Rajendran,
- Yang Hu,
- Alessandro Canella,
- Clayton Peterson,
- Amy Gross,
- Maren Cam,
- Matthew Nazzaro,
- Abigail Haffey,
- Akdes Serin-Harmanci,
- Rosario Distefano,
- Giovanni Nigita,
- Wesley Wang,
- Daniel Kreatsoulas,
- Zihai Li,
- Jesse A. Sepeda,
- Andrew Sas,
- Mark E. Hester,
- Katherine E. Miller,
- Olivier Elemento,
- Ryan D. Roberts,
- Eric C. Holland,
- Ganesh Rao,
- Elaine R. Mardis,
- Prajwal Rajappa
Affiliations
- Sakthi Rajendran
- The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
- Yang Hu
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
- Alessandro Canella
- The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
- Clayton Peterson
- The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
- Amy Gross
- Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
- Maren Cam
- Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
- Matthew Nazzaro
- The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
- Abigail Haffey
- The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
- Akdes Serin-Harmanci
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA
- Rosario Distefano
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Giovanni Nigita
- Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Wesley Wang
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Daniel Kreatsoulas
- Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Zihai Li
- Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Jesse A. Sepeda
- 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
- Andrew Sas
- 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
- Mark E. Hester
- 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, Columbus, OH, USA
- Katherine E. Miller
- The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
- Olivier Elemento
- Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA
- Ryan D. Roberts
- Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
- Eric C. Holland
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Ganesh Rao
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA
- Elaine R. Mardis
- 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, OH, USA
- Prajwal Rajappa
- 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, OH, USA; Corresponding author
- Journal volume & issue
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Vol. 42,
no. 3
p. 112197
Abstract
Summary: 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.
