ArticleNature cancer2023
PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma.
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Article in Nature cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32citing papers in PubMed
14.8field-weighted citation impact, top 1% of its field
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- Endogenous CD155 drives metabolic reprogramming via PI3K/AKT/HIF-1α-glycolysis axis to mediate anti-PD-1 resistance in non-small cell lung cancer.Clinical and translational medicine · 2026Article
- T cell lymphomas: cancers of aberrant immune synapse signalling.Nature reviews. Immunology · 2026Review
- Incidence of B-cell Malignancies in Patients with Lung Cancer Receiving PD-1 Blockade Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Checkpoint inhibitor-induced hematologic immune-related adverse events and their association with disease recurrence in hematolymphoid malignancies: a clinical perspective.Blood research · 2026Review
- Targeting MYC in T-Cell lymphoma via epigenetic modulation with a small-molecule inhibitor.Molecular cancer · 2026Article
- Modulating AP-1 enables CAR T cells to establish an intratumoral stemlike reservoir and overcomes resistance to PD-1 blockade.Science immunology · 2026Article
- Acyl-CoA thioesterases and their derived lipid mediators: linking Acyl-CoA metabolic reprogramming to the tumor microenvironment.Frontiers in immunology · 2026Review
- The Role of Chemokine-Related Genes in Diffuse Large B-Cell Lymphoma Prognosis and Tumor Microenvironment Characteristics.Analytical cellular pathology (Amsterdam) · 2026Article
- Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities.Nature reviews. Clinical oncology · 2025Review
- Cellular profiling identifies targetable T cell phenotypes in lymphocytic variant hypereosinophilic syndrome.The Journal of clinical investigation · 2025Article
- Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.Molecular biomedicine · 2025Review
- Targeting immune microenvironment in cervical cancer: current research and advances.Journal of translational medicine · 2025Review
- Review
- [Immune Checkpoints Mediate Tumor Immune Regulation through Metabolic Pathways].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Characterization of Exhausted T Cell Signatures in Pan-Cancer Settings.International journal of molecular sciences · 2025Article
- SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation.The EMBO journal · 2025Article
- ImmunOctoberfest reloaded.Nature immunology · 2025Article
- Machine Learning-Based Enhanced MRI Radiomics for PDCD1 Prognostication and Expression Prediction in Breast Cancer.Clinical Medicine Insights. Oncology · 2025Article
- Innate Immunity Reimagined: Metabolic Reprogramming as a Gateway to Novel Therapeutics.International journal of biological sciences · 2025Review
- CAR-T cell therapy clinical trials: global progress, challenges, and future directions from ClinicalTrials.gov insights.Frontiers in immunology · 2025Review
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Authors and funding
33 authors at 11 institutions in 5 countries.
Tim Wartewig *TranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany.
Jay Daniels *Department of Biochemistry and Molecular Genetics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0003-4022-6795
Miriam Schulz *TranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany.
Erik HameisterTranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany.
Abhinav JoshiTranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany.
Joonhee ParkDepartment of Biochemistry and Molecular Genetics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Emma MorrishTranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany.
Anuroop V VenkatasubramaniProtein Analysis Unit, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Martinsried, Germany.ORCID 0000-0003-2119-8741
Filippo M CernilogarDepartment of Molecular Biology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Martinsried, Germany.ORCID 0000-0003-2814-3436
Frits H A van HeijsterDepartment of Nuclear Medicine, School of Medicine, Technical University of Munich, Munich, Germany.ORCID 0000-0002-0814-5189
Christian HundshammerDepartment of Nuclear Medicine, School of Medicine, Technical University of Munich, Munich, Germany.
Heike SchneiderInstitute of Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University of Munich, Munich, Germany.
Filippos KonstantinidisTranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany.
Judith V GablerTranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany.
Christine KlementInstitute of Molecular Oncology and Functional Genomics, School of Medicine, Technical University of Munich, Munich, Germany.ORCID 0000-0003-1446-3703
Henry KurniawanExperimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.ORCID 0000-0001-5925-6893
Calvin LawDepartment of Biochemistry and Molecular Genetics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-6784-0085
Yujin LeeDepartment of Biochemistry and Molecular Genetics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-8419-8565
Sara ChoiDepartment of Biochemistry and Molecular Genetics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Joan GuitartDepartment of Dermatology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Ignasi ForneProtein Analysis Unit, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Martinsried, Germany.ORCID 0000-0003-0309-907X
Jérôme GiustinaniInstitut Mondor de Recherche Biomédicale, Inserm U955, Paris-Est Créteil University, Créteil, France.
Markus MüschenCenter of Molecular and Cellular Oncology, Yale School of Medicine, Yale University, New Haven, CT, USA.ORCID 0000-0002-6064-8613
Salvia JainDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
David M WeinstockDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Roland RadInstitute of Molecular Oncology and Functional Genomics, School of Medicine, Technical University of Munich, Munich, Germany.ORCID 0000-0002-6849-9659
Nicolas OrtonneInstitut Mondor de Recherche Biomédicale, Inserm U955, Paris-Est Créteil University, Créteil, France.
Franz SchillingDepartment of Nuclear Medicine, School of Medicine, Technical University of Munich, Munich, Germany.ORCID 0000-0001-5239-4628
Gunnar SchottaDepartment of Molecular Biology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Martinsried, Germany.
Axel ImhofProtein Analysis Unit, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Martinsried, Germany.ORCID 0000-0003-2993-8249
Dirk BrennerExperimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.ORCID 0000-0001-8979-1045
Jaehyuk ChoiDepartment of Biochemistry and Molecular Genetics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. jaehyuk.choi@northwestern.edu.ORCID 0000-0003-2379-2226
Jürgen RulandTranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany. j.ruland@tum.de.ORCID 0000-0002-8381-3597
Technical University of Munich · DENorthwestern University · USCenter for Integrated Protein Science Munich · DEGerman Cancer Research Center · DEInserm · FRLudwig-Maximilians-Universität München · DEYale University · USHarvard University · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USUniversity of Luxembourg · LUUniversity of Southern Denmark · DK
Funding
Metabolic gatekeepers in B-cell malignanciesR35CA197628 · NCI · YALE UNIVERSITY · PI Markus Müschen · 2016 to 2026
$11.7MTargeting oncogenic TCR signaling in PTCLP01CA233412 · NCI · DANA-FARBER CANCER INST · PI MÜSCHEN, MARKUS · 2019 to 2023
$8.7MCARCINOGENESIS TRAINING PROGRAMT32CA009560 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Kathleen Janee Green · 1986 to 2026
$8.4MTargeted activation of autoimmune checkpoints in B cell malignanciesR01CA157644 · NCI · YALE UNIVERSITY · PI Markus Müschen · 2011 to 2026
$5.7MIdentifying Mechanisms Governing T Cell DiversityDP2AI136599 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHOI, JAEHYUK · 2017 to 2017
$2.4MCD25-mediated feedback control of BCR-signaling and its oncogenic mimicsR01CA213138 · NCI · YALE UNIVERSITY · PI MÜSCHEN, MARKUS · 2017 to 2022
$1.9MDissecting mechanisms of resistance underlying CD47-SIRPα inhibition in T-cell lymphomasK08CA230498 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, SALVIA · 2020 to 2024
$1.3MPD-1 tumor suppressor mechanims in peripheral T-cell lymphomaK99CA277586 · NCI · YALE UNIVERSITY · PI WARTEWIG, TIM · 2023 to 2023
$113kDissecting mechanisms by which PD1 deletions drive aggressive cutaneous T cell lymphomaF30CA265107 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DANIELS, JAY · 2021 to 2021
$41kNCI NIH HHS F30 CA265107NCI NIH HHS K08 CA230498NCI NIH HHS K99 CA277586NCI NIH HHS P01 CA233412NCI NIH HHS R01 CA157644NCI NIH HHS R01 CA213138NCI NIH HHS R35 CA197628NCI NIH HHS T32 CA009560NIAID NIH HHS DP2 AI136599
Abstract
The PDCD1-encoded immune checkpoint receptor PD-1 is a key tumor suppressor in T cells that is recurrently inactivated in T cell non-Hodgkin lymphomas (T-NHLs). The highest frequencies of PDCD1 deletions are detected in advanced disease, predicting inferior prognosis. However, the tumor-suppressive mechanisms of PD-1 signaling remain unknown. Here, using tractable mouse models for T-NHL and primary patient samples, we demonstrate that PD-1 signaling suppresses T cell malignancy by restricting glycolytic energy and acetyl coenzyme A (CoA) production. In addition, PD-1 inactivation enforces ATP citrate lyase (ACLY) activity, which generates extramitochondrial acetyl-CoA for histone acetylation to enable hyperactivity of activating protein 1 (AP-1) transcription factors. Conversely, pharmacological ACLY inhibition impedes aberrant AP-1 signaling in PD-1-deficient T-NHLs and is toxic to these cancers. Our data uncover genotype-specific vulnerabilities in PDCD1-mutated T-NHL and identify PD-1 as regulator of AP-1 activity.
Indexed as
Lymphoma, T-CellLymphoma, T-Cell, PeripheralAcetyl Coenzyme AAnimalsGenes, Tumor SuppressorGlycolysisHumansMiceProgrammed Cell Death 1 ReceptorTranscription Factor AP-1Acetyl Coenzyme AProgrammed Cell Death 1 ReceptorTranscription Factor AP-1
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