ArticleThe Journal of clinical investigation2013
Safe TNF-based antitumor therapy following p55TNFR reduction in intestinal epithelium.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 79 citations in OpenAlex.
- Deletion of Astrocytic TNFR1 Attenuates Hyperexcitability and Initiation of Epileptogenesis.Glia · 2026Article
- TNFR1 signaling connects inflammation to impaired fatty acid oxidation to drive intestinal stem cell aging.Nature aging · 2026Article
- Mincle-dependent Th17 adjuvanticity requires TNFR1 signaling in myeloid cells.Frontiers in immunology · 2026Article
- Paracrine Smooth Muscle-to-Endothelial Signaling via TNF Elevates Blood Pressure in Obesity.Circulation research · 2025Article
- Different fibroblast subtypes propel spatially defined ileal inflammation through TNFR1 signalling in murine ileitis.Nature communications · 2025Article
- MLKL-mediated endothelial necroptosis drives vascular damage and mortality in systemic inflammatory response syndrome.Cellular & molecular immunology · 2024Article
- Paneth cell TNF signaling induces gut bacterial translocation and sepsis.Cell host & microbe · 2024Article
- ZBP1 causes inflammation by inducing RIPK3-mediated necroptosis and RIPK1 kinase activity-independent apoptosis.Cell death and differentiation · 2024Article
- Activation and Functions of Col6a1+ Fibroblasts in Colitis-Associated Cancer.International journal of molecular sciences · 2023Article
- cIAPs control RIPK1 kinase activity-dependent and -independent cell death and tissue inflammation.The EMBO journal · 2023Article
- Autoimmune Valvular Carditis Requires Endothelial Cell TNFR1 Expression.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- NEMO- and RelA-dependent NF-κB signaling promotes small cell lung cancer.Cell death and differentiation · 2023Article
- Unveiling the landscape of cytokine research in glioma immunotherapy: a scientometrics analysis.Frontiers in pharmacology · 2023Review
- Selective blood-brain barrier permeabilization of brain metastases by a type 1 receptor-selective tumor necrosis factor mutein.Neuro-oncology · 2022Article
- OTULIN inhibits RIPK1-mediated keratinocyte necroptosis to prevent skin inflammation in mice.Nature communications · 2021Article
- Fundamentally different roles of neuronal TNF receptors in CNS pathology: TNFR1 and IKKβ promote microglial responses and tissue injury in demyelination while TNFR2 protects against excitotoxicity in mice.Journal of neuroinflammation · 2021Article
- NF-κB inhibition in keratinocytes causes RIPK1-mediated necroptosis and skin inflammation.Life science alliance · 2021Article
- Fibroblastic reticular cell lineage convergence in Peyer's patches governs intestinal immunity.Nature immunology · 2021Article
- NF-kappa-B activation unveils the presence of inflammatory hotspots in human gut xenografts.PloS one · 2021Article
- Nidogen 1-Enriched Extracellular Vesicles Facilitate Extrahepatic Metastasis of Liver Cancer by Activating Pulmonary Fibroblasts to Secrete Tumor Necrosis Factor Receptor 1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TNF has remarkable antitumor activities; however, therapeutic applications have not been possible because of the systemic and lethal proinflammatory effects induced by TNF. Both the antitumor and inflammatory effects of TNF are mediated by the TNF receptor p55 (p55TNFR) (encoded by the Tnfrsf1a gene). The antitumor effect stems from an induction of cell death in tumor endothelium, but the cell type that initiates the lethal inflammatory cascade has been unclear. Using conditional Tnfrsf1a knockout or reactivation mice, we found that the expression level of p55TNFR in intestinal epithelial cells (IECs) is a crucial determinant in TNF-induced lethal inflammation. Remarkably, tumor endothelium and IECs exhibited differential sensitivities to TNF when p55TNFR levels were reduced. Tumor-bearing Tnfrsf1a⁺⁺/⁻ or IEC-specific p55TNFR-deficient mice showed resistance to TNF-induced lethality, while the tumor endothelium remained fully responsive to TNF-induced apoptosis and tumors regressed. We demonstrate proof of principle for clinical application of this approach using neutralizing anti-human p55TNFR antibodies in human TNFRSF1A knockin mice. Our results uncover an important cellular basis of TNF toxicity and reveal that IEC-specific or systemic reduction of p55TNFR mitigates TNF toxicity without loss of antitumor efficacy.
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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.