ArticleOncoimmunology2022
IFN-γ activates the tumor cell-intrinsic STING pathway through the induction of DNA damage and cytosolic dsDNA formation.
Article in Oncoimmunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Targeted inhibition of ATR kinase promotes antitumor immunity in HNSCC through enhanced STING activation and T cell function.Translational oncology · 2026Article
- Beyond radiation: immunological potentials of boron neutron capture therapy.Cancer immunology, immunotherapy : CII · 2026Review
- IFI204 drives gasdermin D-mediated mitochondrial permeabilization to amplify neuronal pyroptosis in ischemic stroke.Journal of neuroinflammation · 2026Article
- Carnosic Acid Activates the STING/IRF3 Pathway to Induce Nitric Oxide-Mediated Apoptosis in Osteosarcoma Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Chebulagic acid targets FBXO38 to enhance natural killer cell-mediated anti-tumor immunity in lung adenocarcinoma.Human cell · 2026Article
- IFN-gamma in the tumor microenvironment: dual roles in cancer progression and therapy.EXCLI journal · 2025Review
- Open-label, phase Ia study of STING agonist BI 1703880 plus ezabenlimab for patients with advanced solid tumors.Future oncology (London, England) · 2025Article
- VIM model: a novel model to depict the spatial heterogeneity of the radiation microenvironment.International journal of medical sciences · 2025Review
- cGAS-STING pathway in systemic lupus erythematosus: biological implications and therapeutic opportunities.Immunologic research · 2024Review
- Interferon-induced factor 16 is essential in metastatic melanoma to maintain STING levels and the immune responses upon IFN-γ response pathway activation.Journal for immunotherapy of cancer · 2024Article
- Activation of the cGAS-STING-IRF3 Axis by Type I and II Interferons Contributes to Host Defense.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Tumor cell-directed STING agonist antibody-drug conjugates induce type III interferons and anti-tumor innate immune responses.Nature communications · 2024Article
- The role of IFI16 in regulating PANoptosis and implication in heart diseases.Cell death discovery · 2024Review
- Combination of IFN-gamma with STING agonist and PD-1 immune checkpoint blockade: a potential immunotherapy for gastric cancer.Medical oncology (Northwood, London, England) · 2024Article
- PBMCs as Tool for Identification of Novel Immunotherapy Biomarkers in Lung Cancer.Biomedicines · 2024Article
- Adaptive inhibition of CGAS signaling by TREX1.Trends in cancer · 2024Article
- The potential role of HPV oncoproteins in the PD-L1/PD-1 pathway in cervical cancer: new perspectives on cervical cancer immunotherapy.Frontiers in oncology · 2024Review
- Molecular determinants of immunogenic cell death elicited by radiation therapy.Immunological reviews · 2024Review
- Bidirectional regulation of the cGAS-STING pathway in the immunosuppressive tumor microenvironment and its association with immunotherapy.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stimulator of interferon genes (STING) pathway activation predicts the effectiveness of targeting the PD-1/PD-L1 axis in lung cancer. Active IFN-γ signaling is a common feature in tumors that respond to PD-1/PD-L1 blockade. The connection between IFN-γ and STING signaling in cancer cells has not been documented. We showed that IFN-γ caused DNA damage and the accumulation of cytosolic dsDNA, leading to the activation of the cGAS- and IFI16-dependent STING pathway in lung adenocarcinoma cells. IFN-γ-induced iNOS expression and nitric oxide production were responsible for DNA damage and STING activation. Additional etoposide treatment enhanced IFN-γ-induced IFN-β and CCL5 expression. Tumor-infiltrating T cells stimulated with a combination of anti-CD3 and anti-PD-1 antibodies caused STING activation and increased IFN-β and CCL5 expression in lung adenocarcinoma. These effects were abrogated by the addition of an IFN-γ neutralizing antibody. Our results suggest that the activation of tumor-infiltrating T cells could alter the tumor microenvironment via the IFN-γ-mediated activation of STING signaling in cancer cells.
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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.