ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Low-Dose Ionizing γ-Radiation Elicits the Extrusion of Neutrophil Extracellular Traps.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 15 citations in OpenAlex.
- Tumor-Regional Immune Microenvironment: A Critical Factor in the Design of Radiotherapy-Immunotherapy Combination Trials.International journal of cancer · 2026Review
- Low-dose radiotherapy as an immunomodulator in cancer: dose-specific mechanisms and hybrid high-dose/low-dose strategies.Biomarker research · 2026Review
- Neutrophil extracellular traps in tumor progression: from mechanistic insights and regulatory factors to clinical detection and diagnosis.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Neutrophil extracellular traps drive local tumor progression and metastasis following thermal ablation in liver cancer via TLR9-mediated inflammatory feedback and immunosuppression.Journal for immunotherapy of cancer · 2026Article
- The microbiota-lymphocyte protective axis (MLPA): a novel paradigm for overcoming radiation-induced lymphopenia (RIL) and potentiating the efficacy of tumor immuno-combination therapy.Cancer immunology, immunotherapy : CII · 2026Review
- Radiotherapy and Immune System Interactions Historical Perspectives and Clinical Advancements.Molecular carcinogenesis · 2026Review
- Low-dose radiotherapy synergizes with PD-1 blockade to achieve durable survival in advanced NSCLC through antitumor neutrophil programming.Signal transduction and targeted therapy · 2026Article
- Neutrophil extracellular traps in the tumor microenvironment, metastasis, therapy, and beyond: advances, challenges, and perspectives.Journal of hematology & oncology · 2026Review
- Diallyl disulfide reduces oxidative stress to mitigate uranium tailings radiation-induced damage to the hematopoietic system.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Article
- Calibrating the RT-cGAS-STING axis to drive cold-to-hot tumor transformation: mechanistic foundations and translational strategies for combination with immunotherapy.Molecular cancer · 2026Review
- Radioactive hydrogel with NETs degradation capacity for the boosted tumor radio-immunotherapy.Materials today. Bio · 2026Article
- Ionizing Radiation Induces Extracellular Trap Release from Macrophages.International journal of molecular sciences · 2026Article
- Neutrophil extracellular traps in tumor microenvironment for radiotherapy: friend or foe?Frontiers in immunology · 2026Review
- Advances in Inhaled Nanoparticle Drug Delivery for Pulmonary Disease Management.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Neutrophils and neutrophil extracellular traps: double-edged swords in cancer pathophysiology and therapy resistance.Cell communication and signaling : CCS · 2025Review
- High‑dose X‑ray irradiation induces NETosis via the eCIRP/TREM‑1 axis in mouse neutrophils.International journal of molecular medicine · 2025Article
- Neutrophil Dynamics in Response to Cancer Therapies.Cancers · 2025Review
- Complex I inhibition combined with TLR activation in the breast tumor microenvironment educates cytotoxic neutrophils.Science advances · 2025Article
- New Exploration of Therapeutic Targets for Radiation Pneumonitis: Comparative Analysis of Molecular Pathways in Radiation-Induced and LPS-Induced Pneumonitis.International journal of medical sciences · 2025Review
- Exploring Neutrophil Extracellular Traps in Cardiovascular Pathologies: The Impact of Lipid Profiles, PAD4, and Radiation.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2025Article
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
purposePatients with cancer frequently undergo radiotherapy in their clinical management with unintended irradiation of blood vessels and copiously irrigated organs in which polymorphonuclear leukocytes circulate. Following the observation that such low doses of ionizing radiation are able to induce neutrophils to extrude neutrophil extracellular traps (NET), we have investigated the mechanisms, consequences, and occurrence of such phenomena in patients undergoing radiotherapy. EXPERIMENTAL
designNETosis was analyzed in cultures of neutrophils isolated from healthy donors, patients with cancer, and cancer-bearing mice under confocal microscopy. Cocultures of radiation-induced NETs, immune effector lymphocytes, and tumor cells were used to study the effects of irradiation-induced NETs on immune cytotoxicity. Radiation-induced NETs were intravenously injected to mice for assessing their effects on metastasis. Circulating NETs in irradiated patients with cancer were measured using ELISA methods for detecting MPO-DNA complexes and citrullinated histone 3.
resultsIrradiation of neutrophils with very low γ-radiation doses (0.5-1 Gy) elicits NET formation in a manner dependent on oxidative stress, NADPH oxidase activity, and autocrine IL8. Radiation-induced NETs interfere with NK cell and T-cell cytotoxicity. As a consequence, preinjection of irradiation-induced NETs increases the number of successful metastases in mouse tumor models. Increases in circulating NETs were readily detected in two prospective series of patients following the first fraction of their radiotherapy courses.
conclusionsNETosis is induced by low-dose ionizing irradiation in a neutrophil-intrinsic fashion, and radiation-induced NETs are able to interfere with immune-mediated cytotoxicity. Radiation-induced NETs foster metastasis in mouse models and can be detected in the circulation of patients undergoing conventional radiotherapy treatments. See related commentary by Mowery and Luke, p. 3965.
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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.