ArticleScience advances2023
Proteolytic regulation of CD73 by TRIM21 orchestrates tumor immunogenicity.
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Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
7.4field-weighted citation impact, top 2% of its field
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Who cites it
29 citing papers in PubMed, 32 citations in OpenAlex.
- CD73 inhibition overcomes adaptive immune resistance to PARP inhibition in models of prostate cancer.The Journal of clinical investigation · 2026Article
- Impaired regulation by purinergic signaling axis contributes to CD8+ T cell dysregulation in STAT3 gain of function.JCI insight · 2026Article
- AURKB-mediated phosphorylation of metabolic enzyme CD73 drives immune suppression and renal cell carcinoma progression.Cell death and differentiation · 2026Article
- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- EBV hijacks the metabolic function of CD73 to resist the antitumor function of NK cells.NPJ precision oncology · 2026Article
- Emerging Roles of Adenosine Metabolism in Astrocytes During Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Fluorine-18-Labeled Nucleotide Analogs Targeting Ecto-5'-Nucleotidase (CD73) for Positron Emission Tomography Imaging of Solid Tumors.Angewandte Chemie (International ed. in English) · 2026Article
- Uridine-Cytidine Kinase 2 (UCK2)/Uridine-Cytidine Kinase Like 1 (UCKL1) complex exacerbates the differentiation of myocardial fibroblasts via TRIM21/Smurf2/Smad3 pathway after myocardial infarction.Molecular biomedicine · 2025Article
- Overcoming NK cell resistance in triple-negative breast cancer via adcc with a humanized anti-CD147 antibody.Cancer immunology, immunotherapy : CII · 2025Article
- Overcoming resistance to anti-PD-L1 immunotherapy: mechanisms, combination strategies, and future directions.Molecular cancer · 2025Review
- Salidroside sensitizes Triple-negative breast cancer to ferroptosis by SCD1-mediated lipogenesis and NCOA4-mediated ferritinophagy.Journal of advanced research · 2025Article
- MGAT1-Guided complex N-Glycans on CD73 regulate immune evasion in triple-negative breast cancer.Nature communications · 2025Article
- Targeting the TRIM21-PD-1 axis potentiates immune checkpoint blockade and CAR-T cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- TRIM21: a multifaceted regulator in cancer.Frontiers in cell and developmental biology · 2025Review
- CD73: a new immune checkpoint for leukemia treatment.Frontiers in immunology · 2025Review
- Adenosine receptors on the immuno-oncology expressway: TIME, perspectives, and translation.Frontiers in immunology · 2025Review
- Chaperonin-containing TCP1 subunit 6A inhibition via TRIM21-mediated K48-linked ubiquitination suppresses triple-negative breast cancer progression through the AKT signalling pathway.Clinical and translational medicine · 2024Article
- EPDR1 promotes PD-L1 expression and tumor immune evasion by inhibiting TRIM21-dependent ubiquitylation of IkappaB kinase-β.The EMBO journal · 2024Article
- Tuning Immune-Cold Tumor by Suppressing USP10/B7-H4 Proteolytic Axis Reinvigorates Therapeutic Efficacy of ADCs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.Experimental hematology & oncology · 2024Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Ziyi FuDepartment of Obstetrics and Gynecology, Department of Pharmacology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-8940-2211
Siqi ChenDepartment of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-9498-3823
Yueming ZhuDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USA.ORCID 0000-0002-3101-6238
Donghong ZhangDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USA.ORCID 0000-0003-0190-723X
Ping XieDepartment of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-0891-4953
Qiao JiaoDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USA.ORCID 0000-0001-9113-778X
Junlong ChiDepartment of Obstetrics and Gynecology, Department of Pharmacology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-2650-8756
Shipeng XuDepartment of Obstetrics and Gynecology, Department of Pharmacology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Yifan XueDepartment of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-4068-2707
Xinghua LuDepartment of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-8599-2269
Xinxin SongDepartment of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
Massimo CristofanilliDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0002-4194-7175
William J GradisharDepartment of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Kevin KalinskyWinship Cancer Institute, Emory University School of Medicine, Atlanta, USA.
Yongmei YinDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.ORCID 0000-0003-3335-369X
Bin ZhangDepartment of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-6631-7647
Yong WanDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USA.ORCID 0000-0001-9358-9392
Emory University · USNorthwestern University · USJiangsu Province Hospital · CNRobert H. Lurie Comprehensive Cancer Center of Northwestern UniversityUniversity of Pittsburgh · USCornell University · USSouthwestern Medical Center · US
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MTR&D 7: Cell Specific ProteomicsP41GM108569 · NIGMS · NORTHWESTERN UNIVERSITY · PI KELLEHER, NEIL L · 2015 to 2024
$13.6MInterpretable deep learning models for translational medicine RenewalR01LM012011 · NLM · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Tanner J. Freeman, XINGHUA LU · 2015 to 2026
$3.6MTargeting posttranslational modifications of CD73 in TNBCsR01CA258857 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Yong Wan, Bin Zhang · 2021 to 2026
$3.2MTargeting posttranslational modifications of B7-H4 in carcinogenesis and therapyR01CA258765 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Yong Wan · 2021 to 2026
$2.5MThe distinct role of cysteinyl leukotriene receptor for myeloid-derived suppressive cellsR01CA250101 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ZHANG, BIN · 2020 to 2025
$2.5MTargeting Posttranslational Modifications in Breast CarcinogenesisR01CA250110 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WAN, YONG · 2020 to 2025
$2.3MInterplay between ER and TGF-b in carcinogenesisR01CA202948 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WAN, YONG · 2016 to 2021
$1.4MNCI NIH HHS P30 CA060553NCI NIH HHS R01 CA202948NCI NIH HHS R01 CA250101NCI NIH HHS R01 CA250110NCI NIH HHS R01 CA258765NCI NIH HHS R01 CA258857NIGMS NIH HHS P41 GM108569NLM NIH HHS R01 LM012011
Abstract
Despite the rapid utilization of immunotherapy, emerging challenges to the current immune checkpoint blockade need to be resolved. Here, we report that elevation of CD73 levels due to its aberrant turnover is correlated with poor prognosis in immune-cold triple-negative breast cancers (TNBCs). We have identified TRIM21 as an E3 ligase that governs CD73 destruction. Disruption of TRIM21 stabilizes CD73 that in turn enhances CD73-catalyzed production of adenosine, resulting in the suppression of CD8
Indexed as
ImmunotherapyTriple Negative Breast NeoplasmsCD8-Positive T-LymphocytesHumansProteolysisUbiquitin-Protein LigasesUbiquitin-Protein Ligases
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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.