ArticleThe Journal of clinical investigation2025
Endothelial STING-JAK1 interaction promotes tumor vasculature normalization and antitumor immunity.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Cell-based cancer immunotherapy: milestones, mechanistic insights, and emerging therapeutic directions.Acta pharmacologica Sinica · 2026Review
- cGAS-STING pathway activation drives the cold-to-hot tumor transition and sensitizes immunotherapy.Cancer biology & medicine · 2026Review
- The cGAS/STING pathway in cancer: translating innate DNA sensing into therapeutic potential.The Journal of clinical investigation · 2026Review
- Resetting the immune setpoint of cold tumors through a ferroptosis-cGAS-STING amplification circuit.Journal of translational medicine · 2026Review
- Trimethylamine-producing microbe Bacillus megaterium KCTC 3007 promotes antitumor immunity in endometrial cancer via type I interferon response pathways.Microbiome · 2026Article
- Tumor microenvironment remodeling by STING agonism sensitizes endothelial cells to cytotoxic anti-PD-L1/L2 antibody.Journal of experimental & clinical cancer research : CR · 2026Article
- DNA Methylation-Regulated ZDHHC24 Exacerbates the Risk of Intracranial Aneurysms.Brain and behavior · 2026Article
- GALNT10 Affects O-Glycosylation of IGFBP7 to Promote Tumor Vascular Remodeling and Metastasis of Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A NIR-Ⅱ-Immunostimulatory nanoplatform rewires immunometabolism to unleash STING-driven antitumor immunity.Journal of nanobiotechnology · 2026Article
- Engineered Small Extracellular Vesicles Targeting Tumor-Associated Endothelial Cells to Effectively Remodel the Glioma Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial cell-derived IGFBP7 suppresses angiogenesis and tumor progression in colorectal cancer via the VAPA-TGF-β1 pathway.Journal of experimental & clinical cancer research : CR · 2026Article
- Antitumor effects of STING agonists on nervous system tumors via tumor-intrinsic STING-STAT1-mediated HMGN2 expression.Cancer biology & medicine · 2026Article
- STING synergizes with TOX suppressing HO-1 expression to trigger ferroptosis in tumor-infiltrating CD8+ T cell and immunotherapy resistance.Nature communications · 2026Article
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
- STING-mediated tumor microenvironment remodeling: turning adaptive resistance into therapeutic vulnerability.Frontiers in immunology · 2026Review
- Research on the Mechanism of "Cold Tumor" Formation and Immunotherapy for Its Transformation into "Hot Tumor".Oncology research · 2026Review
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- Endothelial Cell Stimulator of Interferon Genes Regulates IL-6 Production and Is Required for Pathologic Cardiac Hypertrophy and Contractile Dysfunction in Experimental Heart Failure.The American journal of pathology · 2025Article
Corrections and comments
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stimulator of interferon genes (STING) agonists have been developed and tested in clinical trials for their antitumor activity. However, the specific cell population(s) responsible for such STING activation-induced antitumor immunity have not been completely understood. In this study, we demonstrated that endothelial STING expression was critical for STING agonist-induced antitumor activity. STING activation in endothelium promoted vessel normalization and CD8+ T cell infiltration - which required type I IFN (IFN-I) signaling- but not IFN-γ or CD4+ T cells. Rather than an upstream adaptor for inducing IFN-I signaling, STING acted downstream of interferon-α/β receptor (IFNAR) in endothelium for the JAK1-STAT signaling activation. Mechanistically, IFN-I stimulation induced JAK1-STING interaction and promoted JAK1 phosphorylation, which involved STING palmitoylation at the Cysteine 91 site but not its C-terminal tail (CTT) domain. Endothelial STING and JAK1 expression was significantly associated with immune cell infiltration in patients with cancer, and STING palmitoylation level correlated positively with CD8+ T cell infiltration around STING-positive blood vessels in tumor tissues from patients with melanoma. In summary, our findings uncover a previously unrecognized function of STING in regulating JAK1/STAT activation downstream of IFN-I stimulation and provide a new insight for future design and clinical application of STING agonists for cancer therapy.
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