ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06657755 (A Study to Evaluate ENPP1 Expression and Its Role in Immune Evasion and Chemoresistance in Bladder Cancer), which is not on this map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Study to Evaluate ENPP1 Expression and Its Role in Immune Evasion and Chemoresistance in Bladder Cancer
Who cites it
39 citing papers in PubMed, 43 citations in OpenAlex.
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- The Role of cGAS-STING-Driven PANoptosis in Neurodegenerative Diseases and Therapeutic Prospects.Cells · 2026Review
- cGAS-STING pathway activation drives the cold-to-hot tumor transition and sensitizes immunotherapy.Cancer biology & medicine · 2026Review
- LL-37 inhibits osteosarcoma progression by suppressing SQLE-mediated cholesterol synthesis via the PTEN/AKT/mTOR pathway.Journal of bone oncology · 2026Article
- Extracellular vesicle-mediated GALNT1/RPRD1A glycosylation axis drives immune escape and peritoneal metastasis in gastric cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- cGAS-STING pathway in lung cancer and emerging therapeutic approaches.Drug discovery today · 2026Review
- CAR immune cell therapy strategies and advances for lung cancer.Discover oncology · 2026Review
- The role of the cGAS/STING pathway in skeletal muscle regeneration: modulation of inflammation, macrophage polarization, and oxidative stress.Cellular & molecular biology letters · 2026Article
- Sphingosine-1-phosphate promotes CD8 T cell exhaustion in breast cancer via exosomal transfer of TGFBR2.Cell death & disease · 2026Article
- Extracellular vesicle engineering using a small scaffold protein.Nature communications · 2026Article
- Soft-Drug-Inspired MnSTF Nano-Adjuvant for Safe and Synergistic cGAS-STING Activation in Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- Control of poorly immunogenic tumors with systemic STING agonist-loaded liposomes targeting cross-presenting dendritic cells.Clinical & translational immunology · 2026Article
- The cGAS-STING pathway in tumor immunity: dual roles, regulatory mechanisms, and precision therapeutic strategies.Frontiers in pharmacology · 2026Review
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Targeting VCP enhances colorectal cancer therapy through STING stabilization.Journal for immunotherapy of cancer · 2025Article
- JUN-ENPP1-cGAS-STING axis mediates immune evasion and tumor progression in bladder cancer.Journal of translational medicine · 2025Article
- Breaking barriers: The cGAS-STING pathway as a novel frontier in cancer immunotherapy.Cancer communications (London, England) · 2025Review
- The cGAS‒STING pathway in colorectal cancer: bridging innate immunity and therapeutic strategies.Journal of experimental & clinical cancer research : CR · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
To evade immune surveillance, tumor cells express ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) on the surface of their membrane, which degrades extracellular cyclic GMP-AMP (cGAMP), thereby inhibiting the cyclic GMP-AMP synthase (cGAS) stimulator of interferon gene (STING) DNA-sensing pathway. To fully understand this tumor stealth mechanism, it is essential to determine whether other forms of ENPP1 with hydrolytic cGAMP activity also are present in the tumor microenvironment to regulate this innate immune pathway. Herein, it is reported that various tumor-derived exosomes carry ENPP1, and can hydrolyze synthetic 2'3'-cGAMP and endogenous 2'3'-cGAMP produced by cells to inhibit cGAS-STING pathway in immune cells. Moreover, tumor exosomal ENPP1 also can hydrolyze 2'3'-cGAMP bound to LL-37 (an effective transporter of 2'3'-cGAMP) to inhibit STING signaling. Furthermore, high expression of ENPP1 in exosomes is observed isolated from human breast and lung cancer tissue, and tumor exosomal ENPP1 inhibited the immune infiltration of CD8+ T cells and CD4+ T cells. The results elucidate the essential function of tumor exosomal ENPP1 in the cGAS-STING pathway, furthering understanding of the crosstalk between the tumor cells and immune system.
Indexed as
Identifiers
What OpenQuestion holds
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.