Nucleotide metabolism in cancer cells fuels a UDP-driven macrophage cross-talk, promoting immunosuppression and immunotherapy resistance.

Journal

Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119

Informations de publication

Date de publication:
06 Jun 2024
Historique:
received: 05 01 2024
accepted: 23 04 2024
medline: 7 6 2024
pubmed: 7 6 2024
entrez: 6 6 2024
Statut: aheadofprint

Résumé

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

Identifiants

DOI: 10.1038/s43018-024-00771-8 PMID: 38844817
pubmed: 38844817
doi: 10.1038/s43018-024-00771-8
pii: 10.1038/s43018-024-00771-8
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : ImmunoFit, 773208
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : G0A7419N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : 11M9922N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : G0B4620N
Organisme : Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)
ID : 28245
Organisme : European Molecular Biology Organization (EMBO)
ID : SEG9251

Informations de copyright

© 2024. The Author(s).

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Auteurs

Tommaso Scolaro (T)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0002-5739-9425

Marta Manco (M)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0002-0699-4339

Mathieu Pecqueux (M)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Ricardo Amorim (R)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
Life and Health Sciences Research Institute, School of Medicine, University of Minho, Campus de Gualtar, Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.

Rosa Trotta (R)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.

Heleen H Van Acker (HH)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.

Matthias Van Haele (M)

Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
ORCID: 0000-0003-1064-5809

Niranjan Shirgaonkar (N)

Laboratory of Precision Oncology and Cancer Evolution, Genome Institute of Singapore, A*STAR, Singapore, Singapore.
ORCID: 0000-0001-6078-1409

Stefan Naulaerts (S)

Laboratory for Cell Stress & Immunity (CSI), Department of Cellular & Molecular Medicine, KU Leuven, Leuven, Belgium.

Jan Daniluk (J)

Laboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium.
Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
ORCID: 0000-0003-1654-817X

Fran Prenen (F)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0002-5431-1715

Chiara Varamo (C)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.

Donatella Ponti (D)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
Department of Medical-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy.

Ginevra Doglioni (G)

Laboratory of Cellular Metabolism and Metabolic Regulation, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium.
ORCID: 0000-0002-9470-4476

Ana Margarida Ferreira Campos (AM)

Laboratory of Cellular Metabolism and Metabolic Regulation, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium.
ORCID: 0000-0002-8832-7686

Juan Fernandez Garcia (J)

Laboratory of Cellular Metabolism and Metabolic Regulation, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium.
ORCID: 0000-0003-3422-3627

Silvia Radenkovic (S)

Metabolomics Core Facility, Center for Cancer Biology, VIB, Leuven, Belgium.
Metabolomics Core Facility, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.

Pegah Rouhi (P)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.

Aleksandar Beatovic (A)

Unicle Biomedical Data Science, Leuven, Belgium.

Liwei Wang (L)

State 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 Wang (Y)

State 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 Tzoumpa (A)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0003-3733-4090

Asier Antoranz (A)

Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
ORCID: 0000-0001-7284-610X

Ara Sargsian (A)

Translation Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Mario Di Matteo (M)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.

Emanuele Berardi (E)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0002-0775-9605

Jermaine Goveia (J)

Unicle Biomedical Data Science, Leuven, Belgium.
Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.

Bart Ghesquière (B)

Metabolomics Core Facility, Center for Cancer Biology, VIB, Leuven, Belgium.
Metabolomics Core Facility, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0003-1547-1705

Tania Roskams (T)

Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium.

Stefaan Soenen (S)

NanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0003-2390-3133

Thomas Voets (T)

Laboratory of Ion Channel Research (LICR), VIB-KU Leuven Centre for Brain & Disease Research, Leuven, Belgium.
Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.

Bella Manshian (B)

Translation Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Sarah-Maria Fendt (SM)

Laboratory of Cellular Metabolism and Metabolic Regulation, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium.
ORCID: 0000-0001-6018-9296

Peter Carmeliet (P)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium.
Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium.
ORCID: 0000-0001-7961-1821

Abhishek D Garg (AD)

Laboratory for Cell Stress & Immunity (CSI), Department of Cellular & Molecular Medicine, KU Leuven, Leuven, Belgium.
ORCID: 0000-0002-9976-9922

Ramanuj DasGupta (R)

Laboratory of Precision Oncology and Cancer Evolution, Genome Institute of Singapore, A*STAR, Singapore, Singapore.
ORCID: 0000-0001-9015-3729

Baki Topal (B)

Department of Visceral Surgery, KU Leuven and University Hospitals Leuven, Leuven, Belgium.

Massimiliano Mazzone (M)

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium. massimiliano.mazzone@kuleuven.vib.be.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium. massimiliano.mazzone@kuleuven.vib.be.
ORCID: 0000-0001-8824-4015

Classifications MeSH