| First Author | Yang F | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 9 | Pages | eadj4678 |
| PubMed ID | 38416830 | Mgi Jnum | J:345596 |
| Mgi Id | MGI:7609432 | Doi | 10.1126/sciadv.adj4678 |
| Citation | Yang F, et al. (2024) An immunosuppressive vascular niche drives macrophage polarization and immunotherapy resistance in glioblastoma. Sci Adv 10(9):eadj4678 |
| abstractText | Cancer immunity is subjected to spatiotemporal regulation by leukocyte interaction with neoplastic and stromal cells, contributing to immune evasion and immunotherapy resistance. Here, we identify a distinct mesenchymal-like population of endothelial cells (ECs) that form an immunosuppressive vascular niche in glioblastoma (GBM). We reveal a spatially restricted, Twist1/SATB1-mediated sequential transcriptional activation mechanism, through which tumor ECs produce osteopontin to promote immunosuppressive macrophage (Mphi) phenotypes. Genetic or pharmacological ablation of Twist1 reverses Mphi-mediated immunosuppression and enhances T cell infiltration and activation, leading to reduced GBM growth and extended mouse survival, and sensitizing tumor to chimeric antigen receptor T immunotherapy. Thus, these findings uncover a spatially restricted mechanism controlling tumor immunity and suggest that targeting endothelial Twist1 may offer attractive opportunities for optimizing cancer immunotherapy. |
