ArticleNature communications2022
Inhibition of UBA6 by inosine augments tumour immunogenicity and responses.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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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.
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Who cites it
57 citing papers in PubMed, 68 citations in OpenAlex.
- Associations of plasma inosine with lipid parameters in a biracial community cohort.Clinical nutrition (Edinburgh, Scotland) · 2025Trial
- Inosine enhances the efficacy of immune-checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study.Cancer medicine · 2024Trial
- Nuclear OXCT1 attenuates histone β-hydroxybutyrylation-mediated MHC-I transcription.Nature chemical biology · 2026Article
- Molecular pathways linking the gut microbiome to antitumor immunity.Trends in microbiology · 2026Review
- Advances in Exercise-Mediated Regulation of the Gut Microbiota via the Muscle-Gut Axis: Implications for Tumor Immunity and Treatment Responses.Metabolites · 2026Review
- Leveraging gut microbiota for enhanced immune checkpoint blockade in solid tumor therapy.Chinese medical journal · 2026Review
- Decoding the microbiome-immune crosstalk in cancer: from mechanisms to therapeutic translation.Biomarker research · 2026Review
- Gut microbiota and cancer immunotherapy: from dysbiosis to personalized immune checkpoint blockade optimization.Folia microbiologica · 2026Review
- The gut-tumor connection: the role of microbiota in cancer progression and treatment strategies.Journal of advanced research · 2026Review
- UBA6 serves as a prognostic biomarker and promotes tumor progression in pancreatic ductal adenocarcinoma.Translational cancer research · 2026Article
- Uridine restores oocyte quality and mitigates female reproductive aging by inhibition of ferroptosis in mice.Nature communications · 2026Article
- Microbiota-derived metabolites as modulators of cancer immunotherapy response.Nature communications · 2026Review
- Gut Microbiota Biomarkers in Patients with Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors.Life (Basel, Switzerland) · 2026Review
- Effect of supplemental feeding on metabolic profiles and meat quality in yaks: a non-targeted metabolomics approach.Food science of animal resources · 2026Article
- Targeting the gut microbiota-metabolite-immune axis in cancer immunotherapy: mechanistic interplay, therapeutic strategies, and translational applications-a narrative review.Translational cancer research · 2026Review
- Single-cell-based identification of drug synergy with immunotherapy via tumor microenvironment remodeling.Journal for immunotherapy of cancer · 2026Article
- Gut microbiota drives cancer evolution and therapy resistance.Molecular cancer · 2026Review
- Intratumoral microbiota and metabolites: dual roles in cancer progression and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Discovery of the late autophagy inhibitor FZU‑0045‑053 and its anti‑breast cancer and immunomodulatory effects.International journal of oncology · 2026Article
- Inosine alleviates colorectal cancer liver metastasis by promoting M1 macrophage polarization and modulating the PI3K/AKT signaling pathway.Frontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
22 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anti-cancer immunity and response to immune therapy is influenced by the metabolic states of the tumours. Immune checkpoint blockade therapy (ICB) is known to involve metabolic adaptation, however, the mechanism is not fully known. Here we show, by metabolic profiling of plasma samples from melanoma-bearing mice undergoing anti-PD1 and anti-CTLA4 combination therapy, that higher levels of purine metabolites, including inosine, mark ICB sensitivity. Metabolic profiles of ICB-treated human cancers confirm the association between inosine levels and ICB sensitivity. In mouse models, inosine supplementation sensitizes tumours to ICB, even if they are intrinsically ICB resistant, by enhancing T cell-mediated cytotoxicity and hence generating an immunologically hotter microenvironment. We find that inosine directly inhibits UBA6 in tumour cells, and lower level of UBA6 makes the tumour more immunogenic and this is reflected in favourable outcome following ICB therapy in human melanomas. Transplanted mouse melanoma and breast cancer cells with genetic ablation of Uba6 show higher sensitivity to ICB than wild type tumours. Thus, we provide evidence of an inosine-regulated UBA6-dependent pathway governing tumour-intrinsic immunogenicity and hence sensitivity to immune checkpoint inhibition, which might provide targets to overcome ICB resistance.
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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.