Distinct myeloid-derived suppressor cell populations in human glioblastoma.

in Science (New York, N.Y.) by Christina Jackson, Christopher Cherry, Sadhana Bom, Arbor G Dykema, Rulin Wang, Elizabeth Thompson, Ming Zhang, Runzhe Li, Zhicheng Ji, Wenpin Hou, Wentao Zhan, Hao Zhang, John Choi, Ajay Vaghasia, Landon Hansen, William Wang, Brandon Bergsneider, Kate M Jones, Fausto Rodriguez, Jon Weingart, Calixto-Hope Lucas, Jonathan Powell, Jennifer Elisseeff, Srinivasan Yegnasubramanian, Michael Lim, Chetan Bettegowda, Hongkai Ji, Drew Pardoll

TLDR

  • The study identifies specific myeloid-derived suppressor cells (MDSCs) that facilitate glioblastoma progression and mediate tumor immunosuppression, providing new insights for glioblastoma treatment.

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.

Overview

  • The study investigates the role of glioma-associated myeloid cells in tumor growth and immune evasion in glioblastoma.
  • Single-cell RNA sequencing was performed on immune and tumor cells from 33 gliomas to identify distinct myeloid-derived suppressor cell (MDSC) populations.
  • The primary objective is to elucidate the specific MDSCs that facilitate glioblastoma progression and mediate tumor immunosuppression.

Comparative Analysis & Findings

  • Two distinct MDSC populations were identified in IDT-WT glioblastoma: an early progenitor MDSC (E-MDSC) population and a monocytic MDSC (M-MDSC) population.
  • Spatial transcriptomics revealed that E-MDSCs geographically colocalize with metabolic stem-like tumor cells in the pseudopalisading region.
  • Ligand-receptor analysis demonstrated cross-talk between the cells, with glioma stem-like cells producing chemokines attracting E-MDSCs, and E-MDSCs producing growth factors for tumor cells.

Implications and Future Directions

  • The study provides new insights into the specific MDSCs that may facilitate glioblastoma progression and mediate tumor immunosuppression.
  • Future studies could investigate the therapeutic potential of targeting these specific MDSC populations to improve glioblastoma treatment outcomes.
  • The study also highlights the importance of considering the role of MDSCs in glioblastoma progression and immune evasion in future research and clinical trials.
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