ArticleBritish journal of cancer2025
Elucidating the association between TLR-4 expression and the clinical course of glioblastoma leptomeningeal disease.
Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Tumor-intrinsic TLR4 signaling as a context-dependent rheostat in glioblastoma.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundNo treatment exists for leptomeningeal disease (LMD) occurring in a subset of glioblastoma (GBM) patients and portends to a very poor prognosis. This study investigated the association of the Toll-Like Receptor 4 (TLR-4) pro-inflammatory pathway in LMD secondary to GBM.
methodsWe interrogated relevant transcriptomic and proteomic datasets, and primary patient tissue and cerebrospinal fluid (CSF) specimens. To understand translational associations, we introduced a syngeneic murine model and assessed direct TLR-4 antagonism.
resultsTLR-4 was robustly overexpressed in glioma tumors, with a significant survival detriment in GBM specifically. Using single-cell RNA-sequencing, we demonstrated the CSF profile of LMD generally expressed high levels of TLR-4 and enrichment of macrophage immune profile compared to control. In patient specimens, the TLR-4 pathway was significantly expressed in tissue mRNA from GBM LMD (P = 0.020), and increased in CSF from GBM LMD patients compared to controls. TLR-4 antagonism demonstrated favorable anti-tumor effect in multiple GBM cell lines, and significant increase in overall survival in our murine model (median 24 versus 15 days, P = 0.002).
conclusionsTLR-4 expression associates with GBM LMD. TLR-4 antagonism results in anti-cancer effect in vitro and prolonged survival in vivo making it a worthy candidate for further study.
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