ArticleNeoplasia (New York, N.Y.)2023
Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma.
Article in Neoplasia (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Extracellular Matrix-MYCAF Signatures Correlate with Resistance to Neoadjuvant aPD-L1 Immune Checkpoint Inhibition with Durvalumab + Metformin in HPV+ HNSCC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Overcoming Chemoresistance in Glioblastoma: Mechanisms, Therapeutic Strategies, and Functional Precision Medicine.International journal of molecular sciences · 2026Review
- Formation and remodeling of immunological niches in solid tumors: organ-specific architectures, inflammatory parallels, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- Article
- A novel HPβCD-Cu(DDC)Scientific reports · 2025Article
- Single-cell transcriptomic analysis reveals metastatic and immunosuppressive characteristics in meningioma brain-tumor interface.Journal of translational medicine · 2025Article
- A New Tool to Decrease Interobserver Variability in Biomarker Annotation in Solid Tumor Tissue for Spatial Transcriptomic Analysis.Current issues in molecular biology · 2025Article
- An acidic microenvironment promotes lymphatic metastasis of melanoma by Thy-1 in endothelial cells and integrin αvβ3 in tumor cells.Discover oncology · 2025Article
- Sex differences in the molecular profile of adult diffuse glioma are shaped by IDH status and tumor microenvironment.Neuro-oncology · 2025Article
- Protein phosphorylation regulation of key genes in oral squamous cell carcinoma and their role in the immune microenvironment.Frontiers in immunology · 2025Article
- Scoping Review: Methods and Applications of Spatial Transcriptomics in Tumor Research.Cancers · 2024Article
- Exploring the roles of non-coding RNAs in liver regeneration.Non-coding RNA research · 2024Review
- Article
- Revealing the role of SPP1Cell & bioscience · 2024Article
- Multiplexed spatial transcriptomics methods and the application of expansion microscopy.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeGlioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying novel therapeutic opportunities. EXPERIMENTAL
designWe developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR). These specimens were evaluated for treatment response and to identify gene expression pathways driving treatment resistance. Findings were clinically validated using spatial transcriptomics of human GBMs.
resultsThese studies reveal in replicate cohorts, a gene expression profile characterized by upregulation of mesenchymal and stem-like genes at recurrence. Analyses of clinical databases revealed significant association of this transcriptional profile with worse overall survival and upregulation at recurrence. Notably, gene expression analyses identified upregulation of TGFβ signaling, and more than one-hundred-fold increase in THY1 levels at recurrence. Furthermore, THY1-positive cells represented <10% of cells in treatment-naïve tumors, compared to 75-96% in recurrent tumors. We then isolated THY1-positive cells from treatment-naïve patient samples and determined that they were inherently resistant to chemoradiation in orthotopic models. Additionally, using image-guided biopsies from treatment-naïve human GBM, we conducted spatial transcriptomic analyses. This revealed rare THY1+ regions characterized by mesenchymal/stem-like gene expression, analogous to our recurrent mouse model, which co-localized with macrophages within the perivascular niche. We then inhibited TGFBRI activity in vivo which decreased mesenchymal/stem-like protein levels, including THY1, and restored sensitivity to TMZ/IR in recurrent tumors.
conclusionsThese findings reveal that GBM recurrence may result from tumor repopulation by pre-existing, therapy-resistant, THY1-positive, mesenchymal cells within the perivascular niche.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.