ArticleCell death & disease2018
Proton irradiation orchestrates macrophage reprogramming through NFκB signaling.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 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
- The Double-Edged Sword: How Radiotherapy Shapes the Tumor Immune Microenvironment to Modulate Responses to Checkpoint Inhibitors.International journal of molecular sciences · 2026Review
- Article
- Bioresponsive PDA-GelMA hydrogel microspheres coordinate redox-immune homeostasis via controlled rhMUC13 delivery for radiation-induced intestinal injury.Materials today. Bio · 2026Article
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- The link between macrophage polarization and response to radiotherapy in cancers: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Strategic trimodal therapy enhances radiation-induced abscopal response in renal cancer.Journal of translational medicine · 2025Article
- Impacts of Radiation on Metabolism and Vascular Cell Senescence.Antioxidants & redox signaling · 2025Review
- Immunological Effects of Proton Radiotherapy: New Opportunities and Challenges in Cancer Therapy.Cancer innovation · 2025Review
- Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages.Biochemistry and biophysics reports · 2025Article
- HPV-Associated Gene Signatures in Bladder Cancer: A Comprehensive Prognostic Model and its Implications in Immunotherapy.International journal of medical sciences · 2025Article
- Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival.Cancer biology & therapy · 2024Article
- [Role of COX-2/PGE2/EP4 Axis-induced Macrophage Functional Activation in NSCLC Development].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Article
- NF-κB: Governing Macrophages in Cancer.Genes · 2024Review
- Comparative Insight into Microglia/Macrophages-Associated Pathways in Glioblastoma and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Modulation of Innate Immune Memory Dynamics by Subcellular Reactive Oxygen Species.Antioxidants & redox signaling · 2023Review
- Niosomes as Biocompatible Scaffolds for the Multivalent Presentation of Tumor-Associated Antigens (TACAs) to the Immune System.Bioconjugate chemistry · 2023Article
- Tumor-associated macrophages: Prognostic and therapeutic targets for cancer in humans and dogs.Frontiers in immunology · 2023Review
- Noncoding RNA-mediated macrophage and cancer cell crosstalk in hepatocellular carcinoma.Molecular therapy oncolytics · 2022Review
- Dealing with Macrophage Plasticity to Address Therapeutic Challenges in Head and Neck Cancers.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This phenotype contrasts with the M1-like macrophages, which exhibits proinflammatory, phagocytic, and antitumoral functions. As macrophages hold a high plasticity, strategies to orchestrate the reprogramming of M2-like TAMs towards a M1 antitumor phenotype offer potential therapeutic benefits. One of the most used anticancer treatments is the conventional X-ray radiotherapy (RT), but this therapy failed to reprogram TAMs towards an M1 phenotype. While protontherapy is more and more used in clinic to circumvent the side effects of conventional RT, the effects of proton irradiation on macrophages have not been investigated yet. Here we showed that M1 macrophages (THP-1 cell line) were more resistant to proton irradiation than unpolarized (M0) and M2 macrophages, which correlated with differential DNA damage detection. Moreover, proton irradiation-induced macrophage reprogramming from M2 to a mixed M1/M2 phenotype. This reprogramming required the nuclear translocation of NFκB p65 subunit as the inhibition of IκBα phosphorylation completely reverted the macrophage re-education. Altogether, the results suggest that proton irradiation promotes NFκB-mediated macrophage polarization towards M1 and opens new perspectives for macrophage targeting with charged particle therapy.
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