Cancer Cell
Volume 39, Issue 6, 14 June 2021, Pages 779-792.e11
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Article
Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

https://doi.org/10.1016/j.ccell.2021.05.002Get rights and content
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Highlights

  • Macrophages induce the MES-like state of glioblastoma cells

  • Induction is mediated by macrophage-derived OSM interacting with OSMR/LIFR-GP130

  • Subsets of glioblastoma-associated macrophages express a related MES-like program

  • The MES-like state in glioblastoma is associated with cytotoxic T cells programs

Summary

The mesenchymal subtype of glioblastoma is thought to be determined by both cancer cell-intrinsic alterations and extrinsic cellular interactions, but remains poorly understood. Here, we dissect glioblastoma-to-microenvironment interactions by single-cell RNA sequencing analysis of human tumors and model systems, combined with functional experiments. We demonstrate that macrophages induce a transition of glioblastoma cells into mesenchymal-like (MES-like) states. This effect is mediated, both in vitro and in vivo, by macrophage-derived oncostatin M (OSM) that interacts with its receptors (OSMR or LIFR) in complex with GP130 on glioblastoma cells and activates STAT3. We show that MES-like glioblastoma states are also associated with increased expression of a mesenchymal program in macrophages and with increased cytotoxicity of T cells, highlighting extensive alterations of the immune microenvironment with potential therapeutic implications.

Key words

glioblastoma
GBM
scRNA-seq
mesenchymal
tumor microenvironment
macrophage
OSM

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14

Present address: Genentech, 1 DNA Way, South San Francisco, CA, USA

15

These authors contributed equally

16

Senior author

17

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