ArticleScientific reports2019
Ibudilast sensitizes glioblastoma to temozolomide by targeting Macrophage Migration Inhibitory Factor (MIF).
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 50 citations in OpenAlex.
- MIF-Induced CD74+ Microglia and Macrophages Promote Progression of Brain Metastasis and Are Clinically Relevant across Central Nervous System Disorders.Cancer research · 2026Article
- Comprehensive Analysis of scRNA-Seq and RNA-Seq Revealed the Role of Programmed Cell Death-Related Genes in the Prognosis of Glioblastoma Patients.Applied biochemistry and biotechnology · 2026Article
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- Immunosuppressive mechanisms and therapeutic interventions shaping glioblastoma immunity.Nature cancer · 2026Review
- Roles of Macrophage Migration Inhibitory Factor (MIF) Signaling Pathway in Oncovirus Infection and Virus-Associated Cancers.Viruses · 2025Review
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- Exploring tumor-associated macrophages in glioblastoma: from diversity to therapy.NPJ precision oncology · 2025Review
- Single-cell and machine learning integration reveals OS-driven CCND1 promotes an aggressive phenotype in papillary thyroid carcinoma.Frontiers in immunology · 2025Article
- Macrophage migration inhibitory factor-CD74 axis drives vascular smooth muscle cell-induced M1 macrophage polarization to exacerbate intracranial aneurysm inflammation.Frontiers in immunology · 2025Article
- Macrophage migration inhibitory factor (MIF) in CNS diseases: Functional regulation and potential therapeutic indication.Fundamental research · 2024Review
- Integrative analyses of bulk and single-cell RNA-seq reveals the correlation between SPP1Cancer immunology, immunotherapy : CII · 2024Article
- Host derived macrophage migration inhibitory factor expression attenuates anti-tumoral immune cell accumulation and promotes immunosuppression in the tumor microenvironment of head and neck squamous cell carcinoma.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Unveiling the Inflammatory Landscape of Recurrent Glioblastoma through Histological-Based Assessments.Cancers · 2024Review
- Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Revealing the role of SPP1Cell & bioscience · 2024Article
- MIF contribution to progressive brain diseases.Journal of neuroinflammation · 2024Review
- Neuroimmune Support of Neuronal Regeneration and Neuroplasticity following Cerebral Ischemia in Juvenile Mice.Brain sciences · 2023Article
- Immunobiology and Cytokine Modulation of the Pediatric Brain Tumor Microenvironment: A Scoping Review.Cancers · 2023Article
- The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma.JCI insight · 2023Article
- Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recurrence in patients with glioblastoma (GBM) is inevitable resulting in short survival times, even in patients with O-6-Methylguanine-DNA Methyltransferase (MGMT) methylation. Other pathways must be activated to escape from temozolomide (TMZ) treatment, however acquired resistance mechanisms to TMZ are not well understood. Herein, frozen tumors from 36 MGMT methylated patients grouped according to overall survival were extracted and proteins were profiled using surface-enhanced laser desorption/ionization (SELDI) with time-of flight (TOF) proteomics to identify low molecular weight proteins that associated with poor survival outcomes. Overexpression of macrophage migration inhibitory factor (MIF) was identified in human GBM specimens that were MGMT methylated but showed poor survival. This correlation was confirmed in an independent cohort of human GBM. MIF overexpression has been reported in several cancer types, including GBM. We repurposed ibudilast, a specific MIF inhibitor, and treated patient derived cell lines. Ibudilast showed modest anti-proliferative activity however, when combined with TMZ, significant synergism was observed, resulting in cell cycle arrest and apoptosis. In vivo, combined ibudilast and TMZ treatment of a patient derived xenograft (PDX) model resulted in significantly longer overall survival. Our findings have significant clinical implications for people with GBM. Since clinical trials involving ibudilast have shown no adverse side effects and the drug readily penetrates the blood brain barrier, treatment of GBM with this combination is clinically achievable.
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