ArticleJCI insight2024
Potentiating the radiation-induced type I interferon antitumoral immune response by ATM inhibition in pancreatic cancer.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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
16 citing papers in PubMed, 12 citations in OpenAlex.
- Review
- Review
- Review
- Orthogonally targeted tumor radiosensitization using cell penetrating peptide-ATM inhibitor conjugates to stimulate anti-tumor immune responses.bioRxiv : the preprint server for biology · 2026Article
- Radiogenomics and the DNA damage response: opportunities for biomarker-guided radiosensitization in pancreatic cancer.Frontiers in oncology · 2026Review
- DNA damage response inhibitors in pancreatic cancer: progress and challenges.Frontiers in oncology · 2026Review
- Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion.Frontiers in immunology · 2026Review
- Single-Cell Multiomic Profiling Uncovers Radiation Dosage-Sensitive, Cluster-Specific Regulatory Dynamics in Glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Lactate and lactylation in tumor immunity.Frontiers of medicine · 2025Review
- Preclinical evaluation of [European journal of nuclear medicine and molecular imaging · 2025Article
- H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition.Neuro-oncology · 2025Article
- Olaparib and Radiotherapy Induce Type I Interferon- and CD8+ T Cell-Dependent Sensitization to Immunotherapy in Pancreatic Cancer.Molecular cancer therapeutics · 2025Article
- Threading the Needle: Navigating Novel Immunotherapeutics in Pancreatic Ductal Adenocarcinoma.Cancers · 2025Review
- Potential Benefits of Combining Proton or Carbon Ion Therapy with DNA Damage Repair Inhibitors.Cells · 2024Review
- Cytosolic nucleic acid sensors and interferon beta-1 activation drive radiation-induced anti-tumour immune effects in human pancreatic cancer cells.Frontiers in immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Radiotherapy induces a type I interferon-mediated (T1IFN-mediated) antitumoral immune response that we hypothesized could be potentiated by a first-in-class ataxia telangiectasia mutated (ATM) inhibitor, leading to enhanced innate immune signaling, T1IFN expression, and sensitization to immunotherapy in pancreatic cancer. We evaluated the effects of AZD1390 or a structurally related compound, AZD0156, on innate immune signaling and found that both inhibitors enhanced radiation-induced T1IFN expression via the POLIII/RIG-I/MAVS pathway. In immunocompetent syngeneic mouse models of pancreatic cancer, ATM inhibitor enhanced radiation-induced antitumoral immune responses and sensitized tumors to anti-PD-L1, producing immunogenic memory and durable tumor control. Therapeutic responses were associated with increased intratumoral CD8+ T cell frequency and effector function. Tumor control was dependent on CD8+ T cells, as therapeutic efficacy was blunted in CD8+ T cell-depleted mice. Adaptive immune responses to combination therapy provided systemic control of contralateral tumors outside of the radiation field. Taken together, we show that a clinical candidate ATM inhibitor enhances radiation-induced T1IFN, leading to both innate and subsequent adaptive antitumoral immune responses and sensitization of otherwise resistant pancreatic cancer to immunotherapy.
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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.