Distinct myeloid-derived suppressor cell populations in human glioblastoma

Christina Jackson^{1

2

3}, Christopher Cherry⁴, Sadhana Bom^{5

6}, Arbor G Dykema^{5

6}, Rulin Wang^{5

6

7}, Elizabeth Thompson^{5

6}, Ming Zhang^{5

6

7}, Runzhe Li^{5

6

8}, Zhicheng Ji^{5

6

8}, Wenpin Hou^{5

6

8}, Wentao Zhan^{5

6

8}, Hao Zhang⁹, John Choi¹⁰, Ajay Vaghasia^{5

6

7}, Landon Hansen¹⁰, William Wang¹¹, Brandon Bergsneider¹¹, Kate M Jones¹, Fausto Rodriguez¹², Jon Weingart¹⁰, Calixto-Hope Lucas¹², Jonathan Powell^{5

6

7}, Jennifer Elisseeff^{4

5

6}, Srinivasan Yegnasubramanian^{5

6

7}, Michael Lim¹¹, Chetan Bettegowda^{5

7

10}, Hongkai Ji^{5

6

8}, Drew Pardoll^{5

6

7}

Affiliations

¹ Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
² Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³ The Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Translational Tissue Engineering Center, Wilmer Eye Institute, and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, MD, USA.
⁶ Mark Center for Advanced Genomics and Imaging at the Johns Hopkins University, Baltimore, MD, USA.
⁷ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
⁸ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁹ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁰ Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
¹² Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 39818911
DOI: 10.1126/science.abm5214

Distinct myeloid-derived suppressor cell populations in human glioblastoma

Christina Jackson et al. Science. 2025.

. 2025 Jan 17;387(6731):eabm5214.

doi: 10.1126/science.abm5214. Epub 2025 Jan 17.

Authors

Affiliations

¹ Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
² Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³ The Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Translational Tissue Engineering Center, Wilmer Eye Institute, and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, MD, USA.
⁶ Mark Center for Advanced Genomics and Imaging at the Johns Hopkins University, Baltimore, MD, USA.
⁷ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
⁸ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁹ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁰ Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
¹² Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 39818911
DOI: 10.1126/science.abm5214

Abstract

The role of glioma-associated myeloid cells in tumor growth and immune evasion remains poorly understood. We performed single-cell RNA sequencing of immune and tumor cells from 33 gliomas, identifying two distinct myeloid-derived suppressor cell (MDSC) populations in isocitrate dehydrogenase-wild-type (IDT-WT) glioblastoma: an early progenitor MDSC (E-MDSC) population with up-regulation of metabolic and hypoxia pathways and a monocytic MDSC (M-MDSC) population. Spatial transcriptomics demonstrated that E-MDSCs geographically colocalize with metabolic stem-like tumor cells in the pseudopalisading region. Ligand-receptor analysis revealed cross-talk between these cells, where glioma stem-like cells produce chemokines attracting E-MDSCs, which in turn produce growth factors for the tumor cells. This interaction is absent in IDH-mutant gliomas, associated with hypermethylation and repressed gene expression of MDSC-attracting chemokines. Our study elucidates specific MDSCs that may facilitate glioblastoma progression and mediate tumor immunosuppression.

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Update of

Distinct Myeloid Derived Suppressor Cell Populations Promote Tumor Aggression in Glioblastoma.
Jackson C, Cherry C, Bom S, Dykema AG, Thompson E, Zheng M, Ji Z, Hou W, Li R, Zhang H, Choi J, Rodriguez F, Weingart J, Yegnasubramanian S, Lim M, Bettegowda C, Powell J, Eliesseff J, Ji H, Pardoll D. Jackson C, et al. bioRxiv [Preprint]. 2023 Mar 27:2023.03.26.534192. doi: 10.1101/2023.03.26.534192. bioRxiv. 2023. Update in: Science. 2025 Jan 17;387(6731):eabm5214. doi: 10.1126/science.abm5214. PMID: 37034584 Free PMC article. Updated. Preprint.

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Distinct myeloid-derived suppressor cell populations in human glioblastoma

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Distinct myeloid-derived suppressor cell populations in human glioblastoma

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Abstract

Update of

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