ArticleEMBO reports2023
STING agonism turns human T cells into interferon-producing cells but impedes their functionality.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 63 citations in OpenAlex.
- TALAVE in Breast Cancer:bioRxiv : the preprint server for biology · 2026Article
- Caspase-3 cleaves CYLD to restrict interferon signaling during mitochondrial apoptosis.EMBO reports · 2026Article
- The cGAS/STING pathway in cancer: translating innate DNA sensing into therapeutic potential.The Journal of clinical investigation · 2026Review
- cGAS-STING axis: A central regulator of neural homeostasis and neuroinflammatory pathogenesis.Neural regeneration research · 2026Article
- To modify or not to modify: Rethinking mRNA design for CAR T cell engineering.Molecular therapy. Nucleic acids · 2026Article
- A photodynamically activated nanoplatform relieves glucose-driven immunosuppression to potentiate STING immunotherapy in triple-negative breast cancer.Materials today. Bio · 2026Article
- cGAS-STING pathway regulated by spatiotemporal heterogeneity of tumor microenvironment and precision therapy strategies in lung cancer.Journal of experimental & clinical cancer research : CR · 2026Review
- Loss of the autoimmune risk gene TREX1 reveals a convergence of mechanisms promoting immune tolerance loss and antitumor immunity.Science advances · 2026Article
- Methyltransferase SETD7 as a Regulator of STING-Dependent Cytokine Response in Lung Cancer Cells.International journal of molecular sciences · 2026Article
- RIG-I Stimulation Enhances the Effector Function and Proliferation of Primary Human CD8+ T Cells.International journal of molecular sciences · 2026Article
- mRNA-based CAR T cell engineering: Unmodified mRNA enables high CAR expression without innate immune activation in T cells.Molecular therapy. Nucleic acids · 2026Article
- Calibrating the RT-cGAS-STING axis to drive cold-to-hot tumor transformation: mechanistic foundations and translational strategies for combination with immunotherapy.Molecular cancer · 2026Review
- Opportunities and challenges of targeting cGAS-STING in cancer.Nature reviews. Cancer · 2026Review
- Nanostructured branched Y-DNA promotes antitumor immunity through dual activation of cGAS/STING and TLR9.Archives of pharmacal research · 2026Article
- PRRs-Dependent and Independent Mechanisms of STING Signaling in Inflammatory and Autoimmune Diseases.Biomedicines · 2025Review
- Deciphering cGAS-STING signaling: implications for tumor immunity and hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Beyond interferons: Non-canonical roles of MITA/STING.Cell insight · 2025Review
- Overcoming Immune Therapy Resistance in Cancer Through Innate Immune Reprogramming.International journal of molecular sciences · 2025Review
- Recent advances in the structure, function and regulation of the volume-regulated anion channels and their role in immunity.The Journal of physiology · 2025Review
- Emerging Concepts in Immuno-Oncology: Insights from Natural Language Processing-Driven Co-Occurrence Analysis.ACS omega · 2025Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) axis is the predominant DNA sensing system in cells of the innate immune system. However, human T cells also express high levels of STING, while its role and physiological trigger remain largely unknown. Here, we show that the cGAS-STING pathway is indeed functional in human primary T cells. In the presence of a TCR-engaging signal, both cGAS and STING activation switches T cells into type I interferon-producing cells. However, T cell function is severely compromised following STING activation, as evidenced by increased cell death, decreased proliferation, and impaired metabolism. Interestingly, these different phenotypes bifurcate at the level of STING. While antiviral immunity and cell death require the transcription factor interferon regulatory factor 3 (IRF3), decreased proliferation is mediated by STING independently of IRF3. In summary, we demonstrate that human T cells possess a functional cGAS-STING signaling pathway that can contribute to antiviral immunity. However, regardless of its potential antiviral role, the activation of the cGAS-STING pathway negatively affects T cell function at multiple levels. Taken together, these results could help inform the future development of cGAS-STING-targeted immunotherapies.
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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.