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| Home > Publications database > BRAF/MEK inhibition induces cell state transitions boosting immune checkpoint sensitivity in BRAFV600E-mutant glioma. > print |
| Home > Publications database > BRAF/MEK inhibition induces cell state transitions boosting immune checkpoint sensitivity in BRAFV600E-mutant glioma. > print |
| 001 | 302014 | ||
| 005 | 20250623103604.0 | ||
| 024 | 7 | _ | |a 10.1016/j.xcrm.2025.102183 |2 doi |
| 024 | 7 | _ | |a pmid:40505659 |2 pmid |
| 024 | 7 | _ | |a altmetric:178034301 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2025-01212 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Xing, Yao Lulu |b 0 |
| 245 | _ | _ | |a BRAF/MEK inhibition induces cell state transitions boosting immune checkpoint sensitivity in BRAFV600E-mutant glioma. |
| 260 | _ | _ | |a Cambridge, MA |c 2025 |b Cell Press |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1750667717_14031 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a 2025 Jun 17;6(6):102183 |
| 520 | _ | _ | |a Resistance to v-raf murine sarcoma viral oncogene homolog B1 (BRAF) plus mitogen-activated protein kinase kinase (MEK) inhibition (BRAFi+MEKi) in BRAFV600E-mutant gliomas drives rebound, progression, and high mortality, yet it remains poorly understood. This study addresses the urgent need to develop treatments for BRAFi+MEKi-resistant glioma using preclinical mouse models and patient-derived materials. BRAFi+MEKi reveals glioma plasticity by heightening cell state transitions along glial differentiation trajectories, giving rise to astrocyte- and immunomodulatory oligodendrocyte (OL)-like states. PD-L1 upregulation in OL-like cells links cell state transitions to immune evasion, possibly orchestrated by Galectin-3. BRAFi+MEKi induces interferon response signatures, tumor infiltration, and suppression of T cells. Combining BRAFi+MEKi with immune checkpoint inhibition enhances survival in a T cell-dependent manner, reinvigorates T cells, and outperforms individual or sequential therapies in mice. Elevated PD-L1 expression in BRAF-mutant versus BRAF-wild-type glioblastoma supports the rationale for PD-1 inhibition in patients. These findings underscore the potential of targeting glioma plasticity and highlight combination strategies to overcome therapy resistance in BRAFV600E-mutant high-grade glioma. |
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| 650 | _ | 7 | |a BRAF V600E |2 Other |
| 650 | _ | 7 | |a BRAF and MEK inhibitor adaptation |2 Other |
| 650 | _ | 7 | |a Galectin-3 |2 Other |
| 650 | _ | 7 | |a T cell modulation |2 Other |
| 650 | _ | 7 | |a cell state transitions |2 Other |
| 650 | _ | 7 | |a high-grade glioma |2 Other |
| 650 | _ | 7 | |a immune checkpoint inhibition |2 Other |
| 650 | _ | 7 | |a programmed death-ligand 1 |2 Other |
| 700 | 1 | _ | |a Panovska, Dena |b 1 |
| 700 | 1 | _ | |a Park, Jong-Whi |b 2 |
| 700 | 1 | _ | |a Grossauer, Stefan |b 3 |
| 700 | 1 | _ | |a Koeck, Katharina |b 4 |
| 700 | 1 | _ | |a Bui, Brandon |b 5 |
| 700 | 1 | _ | |a Nasajpour, Emon |b 6 |
| 700 | 1 | _ | |a Nirschl, Jeffrey J |b 7 |
| 700 | 1 | _ | |a Feng, Zhi-Ping |b 8 |
| 700 | 1 | _ | |a Cheung, Pierre |b 9 |
| 700 | 1 | _ | |a Habib, Pardes |b 10 |
| 700 | 1 | _ | |a Wei, Ruolun |b 11 |
| 700 | 1 | _ | |a Wang, Jie |b 12 |
| 700 | 1 | _ | |a Thomason, Wes |b 13 |
| 700 | 1 | _ | |a Monje, Michelle |b 14 |
| 700 | 1 | _ | |a Xiu, Joanne |b 15 |
| 700 | 1 | _ | |a Beck, Alexander |b 16 |
| 700 | 1 | _ | |a Weber, Katharina |0 P:(DE-He78)832f5277c0186f22e7704f1930239636 |b 17 |u dkfz |
| 700 | 1 | _ | |a Harter, Patrick N |b 18 |
| 700 | 1 | _ | |a Lim, Michael |b 19 |
| 700 | 1 | _ | |a Mahaney, Kelly B |b 20 |
| 700 | 1 | _ | |a Prolo, Laura M |b 21 |
| 700 | 1 | _ | |a Grant, Gerald A |b 22 |
| 700 | 1 | _ | |a Ji, Xuhuai |b 23 |
| 700 | 1 | _ | |a Walsh, Kyle M |b 24 |
| 700 | 1 | _ | |a Mulcahy Levy, Jean M |b 25 |
| 700 | 1 | _ | |a Hambardzumyan, Dolores |b 26 |
| 700 | 1 | _ | |a Petritsch, Claudia K |b 27 |
| 773 | _ | _ | |a 10.1016/j.xcrm.2025.102183 |g p. 102183 - |0 PERI:(DE-600)3019420-9 |n 6 |p 102183 |t Cell reports / Medicine |v 6 |y 2025 |x 2666-3791 |
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