First Author | Hara T | Year | 2021 |
Journal | Cancer Cell | Volume | 39 |
Issue | 6 | Pages | 779-792.e11 |
PubMed ID | 34087162 | Mgi Jnum | J:347531 |
Mgi Id | MGI:6715728 | Doi | 10.1016/j.ccell.2021.05.002 |
Citation | Hara T, et al. (2021) Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma. Cancer Cell 39(6):779-792.e11 |
abstractText | 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. |