Distinct myeloid-derived suppressor cell populations in human glioblastoma
Christina Jackson, Christopher Cherry, Sadhana Bom, Arbor G. Dykema, Rulin Wang, Elizabeth A. Thompson, Ming Zhang, Runzhe Li, Zhicheng Ji, Wenpin Hou, W. S. Zhan, Hao Zhang, John Choi, Ajay Vaghasia, Landon J. Hansen, William Lee Wang, Brandon Hwa-Lin Bergsneider, Kate M. Jones, Fausto J. Rodríguez, Jon Weingart, Calixto‐Hope G. Lucas, Jonathan D. Powell, Jennifer H. Elisseeff, Srinivasan Yegnasubramanian, Michael Lim, Chetan Bettegowda, Hongkai Ji, Drew M. Pardoll
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.