Distinct myeloid-derived suppressor cell populations in human glioblastoma
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.
Authors
- Runzhe Li (ORCID: https://orcid.org/0000-0002-7851-5392)
- Calixto‐Hope G. Lucas (ORCID: https://orcid.org/0000-0002-8347-9592)
- Michael Lim (ORCID: https://orcid.org/0000-0003-0523-3076)
- Jennifer H. Elisseeff (ORCID: https://orcid.org/0000-0002-5066-1996)
- Hongkai Ji (ORCID: https://orcid.org/0000-0002-6480-0141)
- W. S. Zhan (ORCID: https://orcid.org/0009-0002-1183-5305)
- Jonathan D. Powell (ORCID: https://orcid.org/0000-0002-0850-2852)
- Elizabeth A. Thompson (ORCID: https://orcid.org/0000-0001-8464-9904)
- Christina Jackson (ORCID: https://orcid.org/0000-0003-4210-7976)
- Ajay Vaghasia (ORCID: https://orcid.org/0000-0002-4498-0966)
- Arbor G. Dykema (ORCID: https://orcid.org/0000-0001-5835-3261)
- John Choi (ORCID: https://orcid.org/0000-0002-5162-5903)
- Sadhana Bom (ORCID: https://orcid.org/0009-0007-2194-1511)
- Kate M. Jones (ORCID: https://orcid.org/0009-0002-9921-8669)
- Landon J. Hansen
- Brandon Hwa-Lin Bergsneider (ORCID: https://orcid.org/0000-0001-7013-8150)
- Drew M. Pardoll (ORCID: https://orcid.org/0000-0001-6215-1013)
- Chetan Bettegowda (ORCID: https://orcid.org/0000-0001-9991-7123)
- Wenpin Hou (ORCID: https://orcid.org/0000-0003-0972-2192)
- Christopher Cherry (ORCID: https://orcid.org/0000-0002-5481-0055)
- Zhicheng Ji (ORCID: https://orcid.org/0000-0002-9457-4704)
- Srinivasan Yegnasubramanian (ORCID: https://orcid.org/0000-0003-0744-6606)
- Hao Zhang (ORCID: https://orcid.org/0009-0002-8314-5848)
- Ming Zhang (ORCID: https://orcid.org/0009-0009-7565-3798)
- Fausto J. Rodríguez (ORCID: https://orcid.org/0000-0001-8662-1219)
- Rulin Wang (ORCID: https://orcid.org/0000-0002-6177-1058)
- William Lee Wang (ORCID: https://orcid.org/0000-0002-3121-2415)
- Jon Weingart
Institutions
- Bloomberg (United States) (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Parker Institute for Cancer Immunotherapy (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- University of Pennsylvania (US)
- Stanford University (US)
Publication Details
- Journal
- Science
- Published
- 2025-01-16
- DOI
- https://doi.org/10.1126/science.abm5214
- Citations
- 70
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 55.03