ArticleNature2019
Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade.
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 445 papers.
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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.
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Who cites it
445 citing papers in PubMed, 690 citations in OpenAlex.
- The role of RNA modifications in cancer translational control.RNA biology · 2026Review
- dsRNAscan maps human dsRNAome, revealing conservation, intermolecular dsRNA, and correlates of ADAR dependency.Molecular cell · 2026Article
- Elevated CHAF1A Suppresses Type I Interferon Production and Causes Immunotherapy Resistance in Esophageal Squamous Cell Carcinoma.Cancer immunology research · 2026Article
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- Cancer-Intrinsic Protein Neddylation Modulates the Intratumoral Immune Landscape to Constrain Immune Checkpoint Blockade Therapy.Cancer immunology research · 2026Article
- RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting.Functional & integrative genomics · 2026Review
- Distinguishing self from non-self RNA by editing-specific inosine patterns.Nucleic acids research · 2026Article
- ADAR1 regulates radiosensitivity in ESCC through cIAP2-NF-κB signaling and C16orf46 editing.iScience · 2026Article
- Targeting ADAR1 in Cancer: Biology, Therapeutic Strategies, Challenges, and Limitations.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Article
- ADAR-mediated RNA editing in CNS disorders: from pathogenic mechanisms to therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- Targeting ADAR1 Restores Interferon Signaling and Enhances Immunotherapy Response in Multiple Myeloma.International journal of molecular sciences · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- The regulatory mechanism and clinical significance of RNA editing in prostate cancer.Current urology · 2026Review
- Targeting ADAR1 p150 triggers tumor inhibition and antitumor immunity to overcome immunotherapy resistance.iScience · 2026Article
- A cytoplasmic index for quantifying immune-related A-to-I RNA editing.Genome biology · 2026Article
- Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments.bioRxiv : the preprint server for biology · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Inflammatory cytokines induce new cancer dependencies.Nature genetics · 2026Article
- Z-nucleic acid-mediated PANoptosis in infection, inflammation, and cancer.Communications biology · 2026Review
385 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
Abstract
Most patients with cancer either do not respond to immune checkpoint blockade or develop resistance to it, often because of acquired mutations that impair antigen presentation. Here we show that loss of function of the RNA-editing enzyme ADAR1 in tumour cells profoundly sensitizes tumours to immunotherapy and overcomes resistance to checkpoint blockade. In the absence of ADAR1, A-to-I editing of interferon-inducible RNA species is reduced, leading to double-stranded RNA ligand sensing by PKR and MDA5; this results in growth inhibition and tumour inflammation, respectively. Loss of ADAR1 overcomes resistance to PD-1 checkpoint blockade caused by inactivation of antigen presentation by tumour cells. Thus, effective anti-tumour immunity is constrained by inhibitory checkpoints such as ADAR1 that limit the sensing of innate ligands. The induction of sufficient inflammation in tumours that are sensitized to interferon can bypass the therapeutic requirement for CD8
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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.