ArticleThe Journal of clinical investigation2009
The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers, 2 of them syntheses that pooled it.
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Who cites it
209 citing papers in PubMed, 2 syntheses or guidelines pooled it, 333 citations in OpenAlex.
- Tumor-associated neutrophils suppress CD8British journal of cancer · 2024Pooled it
- Rethinking ovarian cancer: recommendations for improving outcomes.Nature reviews. Cancer · 2011Guideline
- IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Variability in CRP, regulatory T cells and effector T cells over time in gynaecological cancer patients: a study of potential oscillatory behaviour and correlations.Journal of translational medicine · 2014Trial
- Neutrophils in cancer.Nature reviews. Cancer · 2026Review
- Natural killer cells in ovarian cancer therapy: mechanisms, evasion, and therapeutic innovations.Inflammopharmacology · 2026Review
- Unraveling CD4Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- IL1β/IL1R1/IRAK4 Drives Inflammatory Ovarian Cancer Seeding at the inflamed sites and Is Reversed by an IRAK4 inhibitor UR241-2.bioRxiv : the preprint server for biology · 2026Article
- Inflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer.Clinical epigenetics · 2026Review
- Neutrophils in nasopharyngeal carcinoma: from mechanisms to therapeutics.Journal of translational medicine · 2026Review
- EPI-SauriCas9-based mouse ovarian cancer models recapitulating pten deletion in patients.Communications biology · 2025Article
- Inflammasome activation contributes to cisplatin resistance in ovarian cancer.Journal of ovarian research · 2025Article
- Modelling the ageing dependence of cancer evolutionary trajectories.Nature reviews. Cancer · 2025Review
- Neutrophils in cancer: At the crucial crossroads of anti-tumor and pro-tumor.Cancer communications (London, England) · 2025Review
- JAK-STAT-activated, fratricide-resistant CAR-T cells targeting membrane-bound TNF effectively treat AML and solid tumors.Journal for immunotherapy of cancer · 2025Article
- An mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy.Nature communications · 2025Article
- Role of tumor microenvironment in ovarian cancer metastasis and clinical advancements.Journal of translational medicine · 2025Review
- Review
- Bidirectional role of neutrophils in tumor development.Molecular cancer · 2025Review
- Exploring TNFR1: from discovery to targeted therapy development.Journal of translational medicine · 2025Review
149 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
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Cytokines orchestrate the tumor-promoting interplay between malignant cells and the immune system. In many experimental and human cancers, the cytokine TNF-alpha is an important component of this interplay, but its effects are pleiotropic and therefore remain to be completely defined. Using a mouse model of ovarian cancer in which either TNF receptor 1 (TNFR1) signaling was manipulated in different leukocyte populations or TNF-alpha was neutralized by antibody treatment, we found that this inflammatory cytokine maintained TNFR1-dependent IL-17 production by CD4+ cells and that this led to myeloid cell recruitment into the tumor microenvironment and enhanced tumor growth. Consistent with this, in patients with advanced cancer, treatment with the TNF-alpha-specific antibody infliximab substantially reduced plasma IL-17 levels. Furthermore, expression of IL-1R and IL-23R was downregulated in CD4+CD25- cells isolated from ascites of ovarian cancer patients treated with infliximab. We have also shown that genes ascribed to the Th17 pathway map closely with the TNF-alpha signaling pathway in ovarian cancer biopsy samples, showing particularly high levels of expression of genes encoding IL-23, components of the NF-kappaB system, TGF-beta1, and proteins involved in neutrophil activation. We conclude that chronic production of TNF-alpha in the tumor microenvironment increases myeloid cell recruitment in an IL-17-dependent manner that contributes to the tumor-promoting action of this proinflammatory cytokine.
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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.