ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
Systemic inhibition of transforming growth factor-beta in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 118 citations in OpenAlex.
- Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression.The Journal of clinical investigation · 2014Trial
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- Harnessing the role of transforming growth factor-β in glioblastoma: a focus on phytochemicals.Medical oncology (Northwood, London, England) · 2025Review
- Targeting TGF-β signaling in glioblastoma: therapeutic implications and novel drug development strategies.Brain tumor pathology · 2025Review
- Unraveling Glioblastoma Heterogeneity: Advancing Immunological Insights and Therapeutic Innovations.Brain sciences · 2025Review
- The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024Review
- Glioma stem cells remodel immunotolerant microenvironment in GBM and are associated with therapeutic advancements.Cancer biomarkers : section A of Disease markers · 2024Review
- Blocking TGF-β- and Epithelial-to-Mesenchymal Transition (EMT)-mediated activation of vessel-associated mural cells in glioblastoma impacts tumor angiogenesis.Free neuropathology · 2024Article
- T cell exhaustion in malignant gliomas.Trends in cancer · 2023Review
- TGF-β-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine.Nature communications · 2022Article
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- Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma.Cells · 2022Review
- The evolution of the cancer stem cell state in glioblastoma: emerging insights into the next generation of functional interactions.Neuro-oncology · 2021Review
- Cytotoxic T cells isolated from healthy donors and cancer patients kill TGFβ-expressing cancer cells in a TGFβ-dependent manner.Cellular & molecular immunology · 2021Article
- Immunostimulatory silica nanoparticle boosts innate immunity in brain tumors.Nanoscale horizons · 2021Article
- A review of glioblastoma immunotherapy.Journal of neuro-oncology · 2021Review
- Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies.Frontiers in oncology · 2021Review
- Exploiting Radiation Therapy to Restore Immune Reactivity of Glioblastoma.Frontiers in oncology · 2021Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeA variety of cancers, including malignant gliomas, overexpress transforming growth factor-beta (TGF-beta), which helps tumors evade effective immune surveillance through a variety of mechanisms, including inhibition of CD8(+) CTLs and enhancing the generation of regulatory T (T(reg)) cells. We hypothesized that inhibition of TGF-beta would improve the efficacy of vaccines targeting glioma-associated antigen (GAA)-derived CTL epitopes by reversal of immunosuppression. EXPERIMENTAL
designMice bearing orthotopic GL261 gliomas were treated systemically with a TGF-beta-neutralizing monoclonal antibody, 1D11, with or without s.c. vaccinations of synthetic peptides for GAA-derived CTL epitopes, GARC-1 (77-85) and EphA2 (671-679), emulsified in incomplete Freund's adjuvant.
resultsMice receiving the combination regimen exhibited significantly prolonged survival compared with mice receiving either 1D11 alone, GAA vaccines alone, or mock treatments alone. TGF-beta neutralization enhanced the systemic induction of antigen-specific CTLs in glioma-bearing mice. Flow cytometric analyses of brain-infiltrating lymphocytes revealed that 1D11 treatment suppressed phosphorylation of Smad2, increased GAA-reactive/IFN-gamma-producing CD8(+) T cells, and reduced CD4(+)/FoxP3(+) T(reg) cells in the glioma microenvironment. Neutralization of TGF-beta also upregulated plasma levels of interleukin-12, macrophage inflammatory protein-1 alpha, and IFN-inducible protein-10, suggesting a systemic promotion of type-1 cytokine/chemokine production. Furthermore, 1D11 treatment upregulated plasma interleukin-15 levels and promoted the persistence of GAA-reactive CD8(+) T cells in glioma-bearing mice.
conclusionsThese data suggest that systemic inhibition of TGF-beta by 1D11 can reverse the suppressive immunologic environment of orthotopic tumor-bearing mice both systemically and locally, thereby enhancing the therapeutic efficacy of GAA vaccines.
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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.