ArticleJournal for immunotherapy of cancer2022
Harnessing radiotherapy-induced NK-cell activity by combining DNA damage-response inhibition and immune checkpoint blockade.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 66 citations in OpenAlex.
- Dynamic immune profiling predicts response to radiation plus anti-PD-1 therapy in oligometastatic renal cell carcinoma.Nature communications · 2026Trial
- Safety and efficacy of ceralasertib, an ATR kinase inhibitor, combined with olaparib: dose escalation in advanced solid tumours and dose expansion in advanced breast cancer.British journal of cancer · 2026Article
- ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.NPJ precision oncology · 2026Article
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- Gold-incorporated hyaluronic acid nanoparticles enhance ablative radiotherapy efficacy in lung cancer.International journal of pharmaceutics: X · 2026Article
- Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC.British journal of cancer · 2026Article
- ATR kinase inhibitors induce mitochondrial fission in CD8bioRxiv : the preprint server for biology · 2026Article
- PRDM1 Is Associated with Chemoradiotherapy-Associated Enrichment of Adaptive NK Cells in Cervical Cancer.Computational and structural biotechnology journal · 2026Article
- Beyond local control: radiotherapy-immunotherapy combinations fromFrontiers in genetics · 2026Review
- Next-generation immunotherapies for head and neck squamous cell carcinoma: targeting novel immune checkpoints.Annals of medicine · 2025Review
- Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7Oncoimmunology · 2025Article
- Radiation-Induced Immune Responses from the Tumor Microenvironment to Systemic Immunity.Cancers · 2025Review
- H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition.Neuro-oncology · 2025Article
- Development and validation of an immune-related gene signature for the prognostic and immune landscape prediction in head and neck squamous cell carcinoma by integrated analysis of machine learning and Mendelian randomization.Translational cancer research · 2025Article
- Tumor irradiation induced immunogenic response: the impact of DNA damage induction and misrepair.Radiation oncology (London, England) · 2025Review
- Tumor control and immune activation through palliative irradiation and ATR inhibition, PATRIOT Part C: a phase Ib trial.Nature communications · 2025Article
- A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification of a conserved subset of cold tumors responsive to immune checkpoint blockade.Journal for immunotherapy of cancer · 2025Article
- Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment.Research (Washington, D.C.) · 2025Article
- Combination of ataxia telangiectasia and Rad3-related inhibition with ablative radiotherapy remodels the tumor microenvironment and enhances immunotherapy response in lung cancer.Cancer immunology, immunotherapy : CII · 2024Article
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDespite therapeutic gains from immune checkpoint inhibitors (ICI) in many tumor types, new strategies are needed to extend treatment benefits, especially in patients failing to mount effective antitumor T-cell responses. Radiation and drug therapies can profoundly affect the tumor immune microenvironment. Here, we aimed to identify immunotherapies to increase the antitumor response conferred by combined ataxia telangiectasia and Rad3-related kinase inhibition and radiotherapy.
methodsUsing the human papillomavirus (HPV)-negative murine oral squamous cell carcinoma model, MOC2, we assessed the nature of the antitumor response following ataxia telangiectasia and Rad3-related inhibitor (ATRi)/radiotherapy (RT) by performing RNA sequencing and detailed flow cytometry analyses in tumors. The benefit of immunotherapies based on T cell immunoreceptor with Ig and ITIM domains (TIGIT) and Programmed cell death protein 1 (PD-1) immune checkpoint blockade following ATRi/RT treatment was assessed in the MOC2 model and confirmed in another HPV-negative murine oral squamous cell carcinoma model called SCC7. Finally, immune profiling was performed by flow cytometry on blood samples in patients with head and neck squamous cell carcinoma enrolled in the PATRIOT clinical trial of combined ATRi/RT.
resultsATRi enhances radiotherapy-induced inflammation in the tumor microenvironment, with natural killer (NK) cells playing a central role in maximizing treatment efficacy. We demonstrated that antitumor activity of NK cells can be further boosted with ICI targeting TIGIT and PD-1. Analyses of clinical samples from patients receiving ATRi (ceralasertib) confirm the translational potential of our preclinical studies.
conclusionThis work delineates a previously unrecognized role for NK cells in the antitumor immune response to radiotherapy that can be augmented by small-molecule DNA damage-response inhibitors and immune checkpoint blockade.
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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.