ArticleCancer immunology, immunotherapy : CII2014
Combination of an agonistic anti-CD40 monoclonal antibody and the COX-2 inhibitor celecoxib induces anti-glioma effects by promotion of type-1 immunity in myeloid cells and T-cells.
Article in Cancer immunology, immunotherapy : CII, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 111 citations in OpenAlex.
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- Oncolytic HSV-IL27 expression improves CD8 T cell function and therapeutic activity in syngeneic glioma models.Journal for immunotherapy of cancer · 2025Article
- Tumor-infiltrating myeloid cells; mechanisms, functional significance, and targeting in cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Glioma-neuronal circuit remodeling induces regional immunosuppression.Nature communications · 2025Article
- Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy.Current protocols · 2025Article
- Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy.Molecular cancer · 2025Review
- Interferon regulatory factor 8-driven reprogramming of the immune microenvironment enhances antitumor adaptive immunity and reduces immunosuppression in murine glioblastoma.Neuro-oncology · 2024Article
- In vivo mouse models for adult brain tumors: Exploring tumorigenesis and advancing immunotherapy development.Neuro-oncology · 2024Review
- In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma.Genome biology · 2024Article
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- TREM2 function in glioblastoma immune microenvironment: Can we distinguish reality from illusion?Neuro-oncology · 2024Article
- Enhancing CAR-T cell metabolism to overcome hypoxic conditions in the brain tumor microenvironment.JCI insight · 2024Article
- IRF8-driven reprogramming of the immune microenvironment enhances anti-tumor adaptive immunity and reduces immunosuppression in murine glioblastoma.bioRxiv : the preprint server for biology · 2024Article
- Metabolic pathways fueling the suppressive activity of myeloid-derived suppressor cells.Frontiers in immunology · 2024Review
- Exploiting innate immunity for cancer immunotherapy.Molecular cancer · 2023Review
- Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues.International journal of molecular sciences · 2023Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Malignant gliomas are heavily infiltrated by immature myeloid cells that mediate immunosuppression. Agonistic CD40 monoclonal antibody (mAb) has been shown to activate myeloid cells and promote antitumor immunity. Our previous study has also demonstrated blockade of cyclooxygenase-2 (COX-2) reduces immunosuppressive myeloid cells, thereby suppressing glioma development in mice. We therefore hypothesized that a combinatory strategy to modulate myeloid cells via two distinct pathways, i.e., CD40/CD40L stimulation and COX-2 blockade, would enhance anti-glioma immunity. We used three different mouse glioma models to evaluate therapeutic effects and underlying mechanisms of a combination regimen with an agonist CD40 mAb and the COX-2 inhibitor celecoxib. Treatment of glioma-bearing mice with the combination therapy significantly prolonged survival compared with either anti-CD40 mAb or celecoxib alone. The combination regimen promoted maturation of CD11b(+) cells in both spleen and brain, and enhanced Cxcl10 while suppressing Arg1 in CD11b(+)Gr-1(+) cells in the brain. Anti-glioma activity of the combination regimen was T-cell dependent because depletion of CD4(+) and CD8(+) cells in vivo abrogated the anti-glioma effects. Furthermore, the combination therapy significantly increased the frequency of CD8(+) T-cells, enhanced IFN-γ-production and reduced CD4(+)CD25(+)Foxp3(+) T regulatory cells in the brain, and induced tumor-antigen-specific T-cell responses in lymph nodes. Our findings suggest that the combination therapy of anti-CD40 mAb with celecoxib enhances anti-glioma activities via promotion of type-1 immunity both in myeloid cells and T-cells.
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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.