ArticleCancer discovery2021
Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis.
Article in Cancer discovery, 2021. 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 174 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
174 citing papers in PubMed, 269 citations in OpenAlex.
- Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial.Nature medicine · 2025Trial
- ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING-IFN suppression.Cancer biology & therapy · 2026Article
- Metabolites and cancer metastasis.Oncogene · 2026Review
- From initial complete response to recurrence: ENPP1 mutation drives cisplatin resistance through STING/NF-κB/IL-6 axis in hypopharyngeal squamous cell carcinoma.British journal of cancer · 2026Article
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- STING agonist profiling by nucleotide library defines structural determinants of cyclic dinucleotide recognition.iScience · 2026Article
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 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
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- A tumour-host feed-forward loop contributes to the growth of chromosomal instability-induced tumours.EMBO reports · 2026Article
- An siENPP1-Delivering Bimetallic MOF Nanocomplex Enables Triple Activation of the cGAS-STING Pathway for Synergistic Triple-Negative Breast Cancer Therapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Immune-Metabolic Profiling Reveals Functional Heterogeneity Within Colorectal Cancer Consensus Molecular Subtypes.Biology · 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
- Molecular mechanisms regulating cGAS/STING activation in health and disease.The Journal of clinical investigation · 2026Review
- Therapeutic targeting of the cGAS-STING pathway in human disease.The Journal of clinical investigation · 2026Review
- Dexamethasone activates anti-tumor immunity in multiple myeloma by dismantling the GR-PPP1CB complex to restore STING/IRF3 signaling.Journal for immunotherapy of cancer · 2026Article
- A direct, real-time, spectrophotometric assay for measuring ENPP1-catalyzed cGAMP hydrolysis.The Journal of biological chemistry · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
114 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
41 authors at 12 institutions in 5 countries.
Funding
Abstract
Cytosolic DNA is characteristic of chromosomally unstable metastatic cancer cells, resulting in constitutive activation of the cGAS-STING innate immune pathway. How tumors co-opt inflammatory signaling while evading immune surveillance remains unknown. Here, we show that the ectonucleotidase ENPP1 promotes metastasis by selectively degrading extracellular cGAMP, an immune-stimulatory metabolite whose breakdown products include the immune suppressor adenosine. ENPP1 loss suppresses metastasis, restores tumor immune infiltration, and potentiates response to immune checkpoint blockade in a manner dependent on tumor cGAS and host STING. Conversely, overexpression of wild-type ENPP1, but not an enzymatically weakened mutant, promotes migration and metastasis, in part through the generation of extracellular adenosine, and renders otherwise sensitive tumors completely resistant to immunotherapy. In human cancers, ENPP1 expression correlates with reduced immune cell infiltration, increased metastasis, and resistance to anti-PD-1/PD-L1 treatment. Thus, cGAMP hydrolysis by ENPP1 enables chromosomally unstable tumors to transmute cGAS activation into an immune-suppressive pathway. SIGNIFICANCE: Chromosomal instability promotes metastasis by generating chronic tumor inflammation. ENPP1 facilitates metastasis and enables tumor cells to tolerate inflammation by hydrolyzing the immunotransmitter cGAMP, preventing its transfer from cancer cells to immune cells.
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.