ArticleNature cancer2024
Nucleotide metabolism in cancer cells fuels a UDP-driven macrophage cross-talk, promoting immunosuppression and immunotherapy resistance.
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Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51citing papers in PubMed
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Who cites it
51 citing papers in PubMed.
- Resolution and Quantitation of Ribonucleosides and Deoxyribonucleosides in Digested Genomic DNA by UHPLC-MS/MS.Biomedical chromatography : BMC · 2026Article
- Ribonucleotide Reductase Inhibition Triggers Ferroptosis in Genetically Defined Subsets of Non-Small Cell Lung Cancer.Cancer research communications · 2026Article
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Inhibition of (interstitial) P2YPflugers Archiv : European journal of physiology · 2026Article
- Heterogeneity of macrophages in PD-1/PD-L1 inhibitor therapy: a single-cell perspective.Cellular & molecular biology letters · 2026Review
- P2RY6Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Association of Arylacetamide Deacetylase-Mediated Extracellular Matrix Remodeling With Immune Exclusion in Pancreatic Cancer.World journal of oncology · 2026Article
- Metabolic Crosstalk Between Host and Tumor as a Circuit of Resilience in Cancer Therapy.Cells · 2026Review
- The PI3K-Akt-CCND2 axis couples metabolic reprogramming with macrophage M1 polarization.Scientific reports · 2026Article
- Inhibition of (interstitial) P2YResearch square · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Pyrimidinergic calcium signaling links tubular metabolism to fibrosis in kidney disease.Nature communications · 2026Article
- Inhibition of (interstitial) P2YbioRxiv : the preprint server for biology · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Purinergic signal transduction and metabolic regulation by ENTPD5 and ENTPD6.Frontiers in endocrinology · 2026Review
- One-carbon metabolism in cancer immunity: T-cell fitness, epigenetic programming, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Metabolic immune checkpoints in cancer: how tumor-derived metabolites shape immunotherapy resistance.Frontiers in immunology · 2026Review
- Molecular innate immune programs of tumor-associated macrophages in immune checkpoint blockade resistance: a staged framework from suppressive circuitry to translational bottlenecks.Frontiers in immunology · 2026Review
- KRAS-driven cytokine-metabolic crosstalk shapes immune exclusion in pancreatic ductal adenocarcinoma.Frontiers in genetics · 2026Review
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Authors and funding
38 authors.
Tommaso Scolaro *Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0002-5739-9425
Marta Manco *Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0002-0699-4339
Mathieu Pecqueux *Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Ricardo Amorim *Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Rosa TrottaLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Heleen H Van AckerLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Matthias Van HaeleDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.ORCID 0000-0003-1064-5809
Niranjan ShirgaonkarLaboratory of Precision Oncology and Cancer Evolution, Genome Institute of Singapore, A*STAR, Singapore, Singapore.ORCID 0000-0001-6078-1409
Stefan NaulaertsLaboratory for Cell Stress & Immunity (CSI), Department of Cellular & Molecular Medicine, KU Leuven, Leuven, Belgium.
Jan DanilukLaboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium.ORCID 0000-0003-1654-817X
Fran PrenenLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0002-5431-1715
Chiara VaramoLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Donatella PontiLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Ginevra DoglioniLaboratory of Cellular Metabolism and Metabolic Regulation, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0002-9470-4476
Ana Margarida Ferreira CamposLaboratory of Cellular Metabolism and Metabolic Regulation, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0002-8832-7686
Juan Fernandez GarciaLaboratory of Cellular Metabolism and Metabolic Regulation, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0003-3422-3627
Silvia RadenkovicMetabolomics Core Facility, Center for Cancer Biology, VIB, Leuven, Belgium.
Pegah RouhiLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Aleksandar BeatovicUnicle Biomedical Data Science, Leuven, Belgium.
Liwei WangState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.ORCID 0000-0002-8304-3115
Yu WangState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Amalia TzoumpaLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0003-3733-4090
Asier AntoranzDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.ORCID 0000-0001-7284-610X
Ara SargsianTranslation Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Mario Di MatteoLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Emanuele BerardiLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0002-0775-9605
Jermaine GoveiaUnicle Biomedical Data Science, Leuven, Belgium.
Bart GhesquièreMetabolomics Core Facility, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0003-1547-1705
Tania RoskamsDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
Stefaan SoenenNanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.ORCID 0000-0003-2390-3133
Thomas VoetsLaboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium.
Bella ManshianTranslation Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Sarah-Maria FendtLaboratory of Cellular Metabolism and Metabolic Regulation, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0001-6018-9296
Peter CarmelietLaboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID 0000-0001-7961-1821
Abhishek D GargLaboratory for Cell Stress & Immunity (CSI), Department of Cellular & Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID 0000-0002-9976-9922
Ramanuj DasGuptaLaboratory of Precision Oncology and Cancer Evolution, Genome Institute of Singapore, A*STAR, Singapore, Singapore.ORCID 0000-0001-9015-3729
Baki TopalDepartment of Visceral Surgery, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
Massimiliano MazzoneLaboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium. massimiliano.mazzone@kuleuven.vib.be.ORCID 0000-0001-8824-4015
Funding
National Metabolomics Data Repository - nextgen Metabolomics WorkbenchU2CDK119886 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2018 to 2021
$12.7MBiomedical Data Commons Workbench (BDCW)OT2OD030544 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2020 to 2024
$3.2MAssociazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 28245EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ImmunoFit, 773208European Molecular Biology Organization (EMBO) SEG9251Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders) 11M9922NFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) G0A7419NFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) G0B4620NNIDDK NIH HHS U2C DK119886NIH HHS OT2 OD030544
Abstract
Many individuals with cancer are resistant to immunotherapies. Here, we identify the gene encoding the pyrimidine salvage pathway enzyme cytidine deaminase (CDA) among the top upregulated metabolic genes in several immunotherapy-resistant tumors. We show that CDA in cancer cells contributes to the uridine diphosphate (UDP) pool. Extracellular UDP hijacks immunosuppressive tumor-associated macrophages (TAMs) through its receptor P2Y
Indexed as
Drug Resistance, NeoplasmImmunotherapyUridine DiphosphateAnimalsCarcinoma, Pancreatic DuctalCell Line, TumorCytidine DeaminaseHumansImmune ToleranceMacrophagesMiceNucleotidesPancreatic NeoplasmsProgrammed Cell Death 1 ReceptorReceptors, Purinergic P2T-Lymphocytes, CytotoxicCytidine DeaminaseNucleotidesProgrammed Cell Death 1 Receptorpurinoceptor P2Y6Receptors, Purinergic P2Uridine Diphosphate
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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.