ArticleScience translational medicine2024
Intratumoral radiation dose heterogeneity augments antitumor immunity in mice and primes responses to checkpoint blockade.
Article in Science translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
56 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Phase II trial of combination radiation, hormone, and immunotherapy in grade group 5 prostate cancer.Journal for immunotherapy of cancer · 2026Trial
- Unlocking the therapeutic potential of immuno-radiotherapy: insights from preclinical and clinical research.Oncoimmunology · 2026Review
- Heterogeneous Radioimmunotherapy for Bulky Tumors: A Phase 1 Trial for Advanced Non-Small Cell Lung Cancer.Advances in radiation oncology · 2026Article
- Tumor-Regional Immune Microenvironment: A Critical Factor in the Design of Radiotherapy-Immunotherapy Combination Trials.International journal of cancer · 2026Review
- Article
- C-X-C Motif Chemokine Receptor 4 (CXCR4)-Targeted Biologically Guided Proton Spatially Fractionated Radiotherapy for Bulky Limited-Stage Small Cell Lung Cancer.Precision radiation oncology · 2026Article
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- In Situ Vaccination, Low-Dose Targeted Radionuclide Therapy, and Immune Checkpoint Inhibition Eradicate Poorly Immunogenic Metastatic Tumors in Murine Cancer Models.Cancer immunology research · 2026Article
- The future is not always uniform: rethinking radiotherapy through spatial fractionation.Nature reviews. Clinical oncology · 2026Review
- Review
- Immune-preserving radiotherapy and perioperative immunotherapy in stage III NSCLC: a narrative review of current management and future directions for IIIA/IIIB NSCLC.Translational lung cancer research · 2026Review
- Combinatorial Delivery of Low-Dose Radiotherapy and Immunotherapy to Patients with Immune-Excluded Tumors Enhances CD8+ T-cell Functionality.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Spatially fractionated radiotherapy and immunotherapy: a synergistic strategy for systemic anti-tumor immunity.Journal of translational medicine · 2026Review
- SBRT embedded in low-dose RT plus αPD-1 (immuno-EclipseRT, iERT) elicits CD8Nature communications · 2026Article
- Development and characterization of a novel, small animal external beam irradiator using a clinical high dose rate brachytherapy source.Medical physics · 2026Article
- Activation of tumor-specific CD8+ T cells prior to radiopharmaceutical therapy improves antitumor response.Journal for immunotherapy of cancer · 2026Article
- Dosimetric comparison of lattice radiotherapy across three modern linear accelerator platforms.Precision radiation oncology · 2026Article
- The role of the gut microbiota in radiation enteritis: from mechanistic insights to therapeutic applications.Communications biology · 2026Review
- Knowledge mapping of ⁹⁰Y transarterial radioembolization combined with immunotherapy in hepatocellular carcinoma: a bibliometric analysis.Discover oncology · 2026Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Radiation therapy (RT) activates multiple immunologic effects in the tumor microenvironment (TME), with diverse dose-response relationships observed. We hypothesized that, in contrast with homogeneous RT, a heterogeneous RT dose would simultaneously optimize activation of multiple immunogenic effects in a single TME, resulting in a more effective antitumor immune response. Using high-dose-rate brachytherapy, we treated mice bearing syngeneic tumors with a single fraction of heterogeneous RT at a dose ranging from 2 to 30 gray. When combined with dual immune checkpoint inhibition in murine models, heterogeneous RT generated more potent antitumor responses in distant, nonirradiated tumors compared with any homogeneous dose. The antitumor effect after heterogeneous RT required CD4 and CD8 T cells and low-dose RT to a portion of the tumor. At the 3-day post-RT time point, dose heterogeneity imprinted the targeted TME with spatial differences in immune-related gene expression, antigen presentation, and susceptibility of tumor cells to immune-mediated destruction. At a later 10-day post-RT time point, high-, moderate-, or low-RT-dose regions demonstrated distinct infiltrating immune cell populations. This was associated with an increase in the expression of effector-associated cytokines in circulating CD8 T cells. Consistent with enhanced adaptive immune priming, heterogeneous RT promoted clonal expansion of effector CD8 T cells. These findings illuminate the breadth of dose-dependent effects of RT on the TME and the capacity of heterogeneous RT to promote antitumor immunity when combined with immune checkpoint inhibitors.
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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.