ArticleMolecular cancer research : MCR2022
DNA-PK Inhibition and Radiation Promote Antitumoral Immunity through RNA Polymerase III in Pancreatic Cancer.
Article in Molecular cancer research : MCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- 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
- H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition.Neuro-oncology · 2025Article
- Tumor irradiation induced immunogenic response: the impact of DNA damage induction and misrepair.Radiation oncology (London, England) · 2025Review
- Targeting monopolar spindle kinase I (Mps1 or TTK) induces radiosensitization in syngeneic models of triple negative breast cancer (TNBC) and potentiates type I interferon (T1IFN) signaling.Neoplasia (New York, N.Y.) · 2025Article
- DNA-PK Inhibition Shows Differential Radiosensitization in Orthotopic GBM PDX Models Based on DDR Pathway Deficits.Molecular cancer therapeutics · 2025Article
- Olaparib and Radiotherapy Induce Type I Interferon- and CD8+ T Cell-Dependent Sensitization to Immunotherapy in Pancreatic Cancer.Molecular cancer therapeutics · 2025Article
- HPV and p53 Status as Precision Determinants of Head and Neck Cancer Response to DNA-PKcs Inhibition in Combination with Irradiation.Molecular cancer therapeutics · 2025Article
- ARID1A regulates DNA repair through chromatin organization and its deficiency triggers DNA damage-mediated anti-tumor immune response.Nucleic acids research · 2024Article
- Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts.Molecular cancer therapeutics · 2024Article
- Potentiating the radiation-induced type I interferon antitumoral immune response by ATM inhibition in pancreatic cancer.JCI insight · 2024Article
- Phase I study of peposertib and avelumab with or without palliative radiotherapy in patients with advanced solid tumors.ESMO open · 2024Article
- Review
- A genome-wide CRISPR/Cas9 screen identifies DNA-PK as a sensitiser toTheranostics · 2023Article
- Editorial: Targeting DNA damage response to enhance antitumor innate immunity in radiotherapy.Frontiers in oncology · 2023Article
- The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.Frontiers in cell and developmental biology · 2023Review
- Article
- Updates in combined approaches of radiotherapy and immune checkpoint inhibitors for the treatment of breast cancer.Frontiers in oncology · 2022Review
- Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Targeting the DNA damage response in combination with radiation enhances type I interferon (T1IFN)-driven innate immune signaling. It is not understood, however, whether DNA-dependent protein kinase (DNA-PK), the kinase critical for repairing the majority of radiation-induced DNA double-strand breaks in cancer cells, is immunomodulatory. We show that combining radiation with DNA-PK inhibition increases cytosolic double-stranded DNA and tumoral T1IFN signaling in a cyclic GMP-AMP synthase (cGAS)- and stimulator of interferon genes (STING)-independent, but an RNA polymerase III (POL III), retinoic acid-inducible gene I (RIG-I), and antiviral-signaling protein (MAVS)-dependent manner. Although DNA-PK inhibition and radiation also promote programmed death-ligand 1 (PD-L1) expression, the use of anti-PD-L1 in combination with radiation and DNA-PK inhibitor potentiates antitumor immunity in pancreatic cancer models. Our findings demonstrate a novel mechanism for the antitumoral immune effects of DNA-PK inhibitor and radiation that leads to increased sensitivity to anti-PD-L1 in poorly immunogenic pancreatic cancers. IMPLICATIONS: Our work nominates a novel therapeutic strategy as well as its cellular mechanisms pertinent for future clinical trials combining M3814, radiation, and anti-PD-L1 antibody in patients with pancreatic cancer.
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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.