ArticleOncoimmunology
Impaired circulating myeloid CD1c+ dendritic cell function in human glioblastoma is restored by p38 inhibition - implications for the next generation of DC vaccines.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Single-cell transcriptomic analysis deciphers heterogeneity and transcriptional regulatory programs of sepsis with different prognosis.Biology direct · 2026Article
- Tumors located in the brain impair the frequency and phenotype of dendritic cells in blood and tumor.iScience · 2026Article
- The emerging role of dendritic cells in the tumor microenvironment: from antigen presentation to targeted immunotherapy.Cell death & disease · 2025Review
- Rewriting the dendritic cell code in cancer-from subset identity to immunotherapeutic design.FEBS letters · 2025Review
- Insights of immune cell heterogeneity, tumor-initiated subtype transformation, drug resistance, treatment and detecting technologies in glioma microenvironment.Journal of advanced research · 2025Review
- Oligodendroglioma: Advances in Molecular Mechanisms and Immunotherapeutic Strategies.Biomedicines · 2025Review
- Dendritic cells as orchestrators of anticancer immunity and immunotherapy.Nature reviews. Clinical oncology · 2024Review
- Understanding current experimental models of glioblastoma-brain microenvironment interactions.Journal of neuro-oncology · 2024Review
- Targeting the dendritic cell-T cell axis to develop effective immunotherapies for glioblastoma.Frontiers in immunology · 2023Review
- Clinical and Translational Advances in Glioma Immunotherapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Review
- Detection of Specific Immune Cell Subpopulation Changes Associated with Systemic Immune Inflammation-Index Level in Germ Cell Tumors.Life (Basel, Switzerland) · 2022Article
- Article
- Targeting Glioblastoma: The Current State of Different Therapeutic Approaches.Current neuropharmacology · 2021Review
- Regulation of autophagy by canonical and non-canonical ER stress responses.Seminars in cancer biology · 2020Review
- Peripherally-sourced myeloid antigen presenting cells increase with advanced aging.Brain, behavior, and immunity · 2020Article
- Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications.International journal of molecular sciences · 2020Review
- Resistance Mechanisms and Barriers to Successful Immunotherapy for Treating Glioblastoma.Cells · 2020Review
- Enhancing the efficacy of immunotherapy using radiotherapy.Clinical & translational immunology · 2020Review
- Immunotherapeutic early-phase clinical trials and malignant gliomas: A single-center experience and comprehensive immunophenotyping of circulating leukocytes.Neuro-oncology advancesArticle
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Current treatments for glioblastoma (GBM) have limited efficacy and significant morbidity and therefore new strategies are urgently needed. Dendritic cells have the power to create anti-tumor immune responses. The greater potency of circulating dendritic cells (DC) over laboratory-generated monocyte-derived DC makes them exciting new immunotherapeutic candidates. To determine the immune status of GBM patients we initially investigated the frequency and function of circulating DC subsets. Furthermore, we tested the therapeutic potential of inhibiting the p38 mitogen-activated protein kinase pathway (p38i) in circulating DC to overcome DC dysfunction. GBM patients (n = 16) had significantly reduced numbers of the major myeloid circulating dendritic cell (cDC2) and plasmacytoid DC vs healthy controls; 1736 vs 4975 (p = 0.028) and 893 vs 2287 cells/mL (P = <0.001) respectively. This inversely correlated with dexamethasone (Dex) dose in a log-linear model, and disease status. Patients' cDC2 were immature with impaired interleukin (IL)-12 secretion, reduced IL-12:IL-10 ratio, and low HLA-DR and CD86 expression. Exposure of healthy donor cDC2 to Dex or GBM cell lysate resulted in a similar low IL-12:IL-10 ratio. Inhibition of p38 restored the IL-12:IL-10 balance in Dex or tumor lysate-conditioned healthy cDC2 and enhanced T-cell proliferation and interferon-gamma (IFNγ) production. Importantly, patient-derived cDC2 showed a similar reversal of DC dysfunction with p38i. This study demonstrates the therapeutic potential of developing the next generation of DC vaccines using enhanced p38i-conditioned cDC2. We will therefore shortly embark on a clinical trial of adoptively transferred, p38 MAPK-inhibited cDC2 in adults with GBM.
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