ArticleCancer immunology research2016
Synergistic COX2 Induction by IFNγ and TNFα Self-Limits Type-1 Immunity in the Human Tumor Microenvironment.
Article in Cancer immunology research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 66 citations in OpenAlex.
- Phase II Trial of Adjuvant Dendritic Cell Vaccine in Combination with Celecoxib, Interferon-α, and Rintatolimod in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases.Annals of surgical oncology · 2021Trial
- Salvianolic acid monomers against metastasis: Decoding the multilayered interception of EMT, angiogenesis and immune evasion (Review).International journal of molecular medicine · 2026Review
- Role of the tumor microenvironment in chemotherapy resistance in ovarian cancer and targeted therapy.Journal of ovarian research · 2025Review
- Is dystrophin immunogenicity a barrier to advancing gene therapy for Duchenne muscular dystrophy?Gene therapy · 2025Review
- Synergy between TLR3-ligand and IFN-α in the transient sensitization of "Cold" tumors to PD-1 blockade and the induction of systemic immunity.Journal for immunotherapy of cancer · 2025Article
- Paclitaxel, interferons and functional reprogramming of tumor-associated macrophages in optimized chemo-immunotherapy.Journal for immunotherapy of cancer · 2025Review
- MDSC checkpoint blockade therapy: a new breakthrough point overcoming immunosuppression in cancer immunotherapy.Cancer gene therapy · 2025Review
- Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies.Theranostics · 2025Review
- IFNγ-mediated suppression of alternative NF-κB in tumor-resident myeloid cells promotes selective recruitment of cytotoxic but not regulatory T cells.Frontiers in immunology · 2025Article
- Meeting Highlights The 4th Marie Skłodowska-Curie Symposium on cancer research and care: Mechanisms of support for regional & international collaborations.Wiadomosci lekarskie (Warsaw, Poland : 1960) · 2025Article
- Systemic chemokine-modulatory regimen combined with neoadjuvant chemotherapy in patients with triple-negative breast cancer.Journal for immunotherapy of cancer · 2024Article
- Engineering dendritic cell biomimetic membrane as a delivery system for tumor targeted therapy.Journal of nanobiotechnology · 2024Review
- Dendritic Cell Plasticity, Radiation, and Newton's Third Law.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Review
- Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment.Exploration of targeted anti-tumor therapy · 2024Review
- Drug Repurposing for Targeting Myeloid-Derived Suppressor-Cell-Generated Immunosuppression in Ovarian Cancer: A Literature Review of Potential Candidates.Pharmaceutics · 2023Review
- Crosstalk of Immune Cells and Platelets in an Ovarian Cancer Microenvironment and Their Prognostic Significance.International journal of molecular sciences · 2023Review
- Review
- Targeting the immune microenvironment for ovarian cancer therapy.Frontiers in immunology · 2023Review
- Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets.Journal of hematology & oncology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Maintenance of CTL-, Th1-, and NK cell-mediated type-1 immunity is essential for effective antitumor responses. Unexpectedly, we observed that the critical soluble mediators of type-1 immune effector cells, IFNγ and TNFα, synergize in the induction of cyclooxygenase 2 (COX2), the key enzyme in prostaglandin (PG)E2 synthesis, and the subsequent hyperactivation of myeloid-derived suppressor cells (MDSC) within the tumor microenvironment (TME) of ovarian cancer patients. MDSC hyperactivation by type-1 immunity and the resultant overexpression of indoleamine 2,3-dioxygenase (IDO), inducible nitric oxide synthase (iNOS/NOS2), IL10, and additional COX2 result in strong feedback suppression of type-1 immune responses. This paradoxical immune suppression driven by type-1 immune cell activation was found to depend on the synergistic action of IFNγ and TNFα, and could not be reproduced by either of these factors alone. Importantly, from a therapeutic standpoint, these negative feedback limiting type-1 responses could be eliminated by COX2 blockade, allowing amplification of type-1 immunity in the ovarian cancer TME. Our data demonstrate a new mechanism underlying the self-limiting nature of type-1 immunity in the human TME, driven by the synergistic induction of COX2 by IFNγ and TNFα, and provide a rationale for targeting the COX2-PGE2 axis to enhance the effectiveness of cancer immunotherapies.
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Registered trials
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