ArticleCancer research2018
Activation of the Receptor Tyrosine Kinase AXL Regulates the Immune Microenvironment in Glioblastoma.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 140 citations in OpenAlex.
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Tumor-Suppressive microRNA Therapy Inhibits Growth of Glioblastoma Multiforme Xenografts.Cancers · 2026Article
- TYRO3, AXL, MERTK and Their Ligands in Brain Metastases From Colorectal Cancers.Cancer medicine · 2026Article
- Review
- Increased CSF levels of soluble AXL at diagnosis correlate with poor prognosis in patients affected by amyotrophic lateral sclerosis.Brain communications · 2026Article
- Pericytes orchestrate a tumor-restraining microenvironment in glioblastoma.Nature communications · 2025Article
- Paratope mapping of tilvestamab, an anti-AXL function-blocking antibody, using high-throughput bacterial expression of secreted scFv-osmY fusion proteins.Bioscience reports · 2025Article
- The Receptor Tyrosine Kinase Axl in (Advanced) Gastric Cancer-From Pathophysiology to Therapeutic Impact.Medicina (Kaunas, Lithuania) · 2025Review
- Development and validation of a prognostic prediction model based on coagulation-related genes and clinical factors in acute leukemia.Translational pediatrics · 2025Article
- PROS1-MERTK Axis Drives Tumor Microenvironment Crosstalk and Progression in Papillary Thyroid Microcarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inhibition of FOXM1 Leads to Suppression of Cell Proliferation, Migration, and Invasion Through AXL/eEF2 Kinase Signaling and Induces Apoptosis and Ferroptosis in GBM Cells.International journal of molecular sciences · 2025Article
- Exploring tumor-associated macrophages in glioblastoma: from diversity to therapy.NPJ precision oncology · 2025Review
- Current Research Trends in Glioblastoma: Focus on Receptor Tyrosine Kinases.International journal of molecular sciences · 2025Review
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Single-cell and machine learning integration reveals OS-driven CCND1 promotes an aggressive phenotype in papillary thyroid carcinoma.Frontiers in immunology · 2025Article
- From Bench to Bedside: A Team's Approach to Multidisciplinary Strategies to Combat Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma.Journal of clinical medicine · 2024Review
- AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.Experimental hematology & oncology · 2024Review
- Spatial computational modelling illuminates the role of the tumour microenvironment for treating glioblastoma with immunotherapies.NPJ systems biology and applications · 2024Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 10 institutions in 5 countries.
Funding
Abstract
Glioblastoma (GBM) is a lethal disease with no effective therapies available. We previously observed upregulation of the TAM (Tyro-3, Axl, and Mer) receptor tyrosine kinase family member AXL in mesenchymal GBM and showed that knockdown of AXL induced apoptosis of mesenchymal, but not proneural, glioma sphere cultures (GSC). In this study, we report that BGB324, a novel small molecule inhibitor of AXL, prolongs the survival of immunocompromised mice bearing GSC-derived mesenchymal GBM-like tumors. We show that protein S (PROS1), a known ligand of other TAM receptors, was secreted by tumor-associated macrophages/microglia and subsequently physically associated with and activated AXL in mesenchymal GSC. PROS1-driven phosphorylation of AXL (pAXL) induced NFκB activation in mesenchymal GSC, which was inhibited by BGB324 treatment. We also found that treatment of GSC-derived mouse GBM tumors with nivolumab, a blocking antibody against the immune checkpoint protein PD-1, increased intratumoral macrophages/microglia and activation of AXL. Combinatorial therapy with nivolumab plus BGB324 effectively prolonged the survival of mice bearing GBM tumors. Clinically, expression of AXL or PROS1 was associated with poor prognosis for patients with GBM. Our results suggest that the PROS1-AXL pathway regulates intrinsic mesenchymal signaling and the extrinsic immune microenvironment, contributing to the growth of aggressive GBM tumors.
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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.