ArticleCell death and differentiation2017
NOX2-dependent ATM kinase activation dictates pro-inflammatory macrophage phenotype and improves effectiveness to radiation therapy.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Modulation of tumor-associated macrophage activity with radiation therapy: a systematic review.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Pooled it
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- Life-span-dependent transcriptional dynamics of the human heart.Science advances · 2026Article
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- The Implications of Radiotherapy-Induced Cellular Senescence for Cancer Treatment and Tumor Microenvironment Modulation.International journal of biological sciences · 2026Review
- The role of macrophages in radiation-induced lung injury: from pathological mechanisms to therapeutic targets.Frontiers in immunology · 2026Review
- Towards a personalized utilization of stereotactic body radiotherapy for the management of liver metastases in solid tumors.Cancer metastasis reviews · 2025Review
- Role of Renin-Angiotensin System and Macrophages in Breast Cancer Microenvironment.Diseases (Basel, Switzerland) · 2025Article
- Reactive Oxygen Species: From Tumorigenesis to Therapeutic Strategies in Cancer.Cancer medicine · 2025Review
- Mechanisms of Action of AGuIX as a Pan-Cancer Nano-Radiosensitizer: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Identification and validation of biomarkers related to ferroptosis in idiopathic pulmonary fibrosis.Scientific reports · 2025Article
- Loss of Cullin 5 in myeloid cells protects against autoimmune neuroinflammation.Frontiers in immunology · 2025Article
- Efficacy and pharmacodynamic effect of anti-CD73 and anti-PD-L1 monoclonal antibodies in combination with cytotoxic therapy: observations from mouse tumor models.Cancer biology & therapy · 2024Article
- Chemoradiotherapy-induced ACKR2Cell reports. Medicine · 2024Article
- The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.Current cancer drug targets · 2024Review
- Metabolism, metabolites, and macrophages in cancer.Journal of hematology & oncology · 2023Review
- Effects of glycolysis on the polarization and function of tumor‑associated macrophages (Review).International journal of oncology · 2023Review
- Radioimmunotherapy Targeting B7-H3International journal of biological sciences · 2023Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although tumor-associated macrophages have been extensively studied in the control of response to radiotherapy, the molecular mechanisms involved in the ionizing radiation-mediated activation of macrophages remain elusive. Here we show that ionizing radiation induces the expression of interferon regulatory factor 5 (IRF5) promoting thus macrophage activation toward a pro-inflammatory phenotype. We reveal that the activation of the ataxia telangiectasia mutated (ATM) kinase is required for ionizing radiation-elicited macrophage activation, but also for macrophage reprogramming after treatments with γ-interferon, lipopolysaccharide or chemotherapeutic agent (such as cisplatin), underscoring the fact that the kinase ATM plays a central role during macrophage phenotypic switching toward a pro-inflammatory phenotype through the regulation of mRNA level and post-translational modifications of IRF5. We further demonstrate that NADPH oxidase 2 (NOX2)-dependent ROS production is upstream to ATM activation and is essential during this process. We also report that the inhibition of any component of this signaling pathway (NOX2, ROS and ATM) impairs pro-inflammatory activation of macrophages and predicts a poor tumor response to preoperative radiotherapy in locally advanced rectal cancer. Altogether, our results identify a novel signaling pathway involved in macrophage activation that may enhance the effectiveness of radiotherapy through the reprogramming of tumor-infiltrating macrophages.
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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.