ArticleNature communications2021
Synergistic immunotherapy of glioblastoma by dual targeting of IL-6 and CD40.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
102 citing papers in PubMed, 2 syntheses or guidelines pooled it, 149 citations in OpenAlex.
- The Association Between CD40 rs1883832 Polymorphism and Cancer Susceptibility: A Systematic Review and Meta-Analysis.Cancer medicine · 2026Pooled it
- Impact of molecular and clinical variables on survival outcome with immunotherapy for glioblastoma patients: A systematic review and meta-analysis.CNS neuroscience & therapeutics · 2022Pooled it
- Article
- Advances in the role of astrocytes in glioma progression and therapy.Acta pharmacologica Sinica · 2026Review
- IL6 Supports Development of an Immunosuppressive Microenvironment and Resistance to Therapy in Glioblastoma.Cancer research · 2026Article
- Cannabidiol- and Celecoxib-Loaded Liposomes as a Strategy to Modulate Redox and Inflammatory Signaling in High-Grade Glioma: A Preliminary In Vivo Study.International journal of molecular sciences · 2026Article
- Diphenyl Diselenide and Temozolomide: Downregulation of Inflammatory, Redox, and Tumor-Associated Pathways in Glioblastoma.Biological trace element research · 2026Article
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- A trispecific antibody engaging T cells with tumour and myeloid cells augments antitumour immunity.Nature biomedical engineering · 2026Article
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Review
- The promise of immunotherapy for central nervous system tumours.Nature reviews. Immunology · 2026Review
- Insights into the structural differences between homo- and heterodimers enriched from a cocktail of monoclonal antibodies against SARS-CoV-2.Scientific reports · 2026Article
- Metabolic reprogramming and immunosenescence: a new sight for glioma therapy.Frontiers in cell and developmental biology · 2026Review
- Next-generation immunotherapy biologics for glioblastoma.Frontiers in immunology · 2026Review
- AI-based pathomics model predicts regulatory T cell infiltration and radiotherapy response in IDH-wild-type glioblastoma.Frontiers in immunology · 2026Article
- Quantitative Cell Type-Specific Immunopeptidome Analysis of Macrophage and Tumor Coevolution Reveals Therapeutic MHC-I Peptides in Glioblastoma.Cancer research · 2025Article
- METTL14 Regulates the Expression of Genes Related to Interferon, Interleukin and MHC Class I in Nasopharyngeal Carcinoma Cells.Cancer medicine · 2025Article
- PD-L1 autoregulation promotes the proliferation, migration and invasion of glioblastoma cells via GP130/JAK2/STAT3/IRAK2/IL6 signaling pathway.Scientific reports · 2025Article
- Novel oncolytic adenovirus-based PEPvIII vaccine displays a super antitumor effect in glioma models.Journal for immunotherapy of cancer · 2025Article
- Oncolytic virus-mediated immunomodulation in glioblastoma: Insights from clinical trials and challenges.Seminars in immunology · 2025Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Immunologically-cold tumors including glioblastoma (GBM) are refractory to checkpoint blockade therapy, largely due to extensive infiltration of immunosuppressive macrophages (Mϕs). Consistent with a pro-tumor role of IL-6 in alternative Mϕs polarization, we here show that targeting IL-6 by genetic ablation or pharmacological inhibition moderately improves T-cell infiltration into GBM and enhances mouse survival; however, IL-6 inhibition does not synergize PD-1 and CTLA-4 checkpoint blockade. Interestingly, anti-IL-6 therapy reduces CD40 expression in GBM-associated Mϕs. We identify a Stat3/HIF-1α-mediated axis, through which IL-6 executes an anti-tumor role to induce CD40 expression in Mϕs. Combination of IL-6 inhibition with CD40 stimulation reverses Mϕ-mediated tumor immunosuppression, sensitizes tumors to checkpoint blockade, and extends animal survival in two syngeneic GBM models, particularly inducing complete regression of GL261 tumors after checkpoint blockade. Thus, antibody cocktail-based immunotherapy that combines checkpoint blockade with dual-targeting of IL-6 and CD40 may offer exciting opportunities for GBM and other solid tumors.
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What OpenQuestion holds
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.