ArticleThe Journal of clinical investigation2024
Pharmacological suppression of the OTUD4/CD73 proteolytic axis revives antitumor immunity against immune-suppressive breast cancers.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 27 citations in OpenAlex.
- Loss of NCCRP1 overcomes immune evasion in lung adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- OTUD4 regulates pancreatic cancer progression via Hippo/YAP axis.Neoplasia (New York, N.Y.) · 2026Article
- OTUD4 deubiquitination stabilizes EGFR and activates the PI3K/AKT pathway to promote the invasiveness of triple-negative breast cancer.Cell death & disease · 2026Article
- OTU deubiquitinases as immune-circuit editors: from human immunopathology to therapeutic prioritization.Frontiers in immunology · 2026Review
- Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.Frontiers in oncology · 2026Review
- OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026Review
- Review
- OTUD4 suppresses colorectal cancer progression through deubiquitinating p53.Discover oncology · 2025Article
- Druggable genome CRISPR screening identifies the KEAP1/NRF2 axis as a mediator of PD-L1 expression.Communications biology · 2025Article
- Spatial omics technology potentially promotes the progress of tumor immunotherapy.British journal of cancer · 2025Review
- Spatial Transcriptomics Decodes Breast Cancer Microenvironment Heterogeneity: From Multidimensional Dynamic Profiling to Precision Therapy Blueprint Construction.Biomolecules · 2025Review
- Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dissecting the dual role of OTU family proteins in tumor progression and immune escape.Frontiers in immunology · 2025Review
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- Oncolytic Virus Therapy in a New Era of Immunotherapy, Enhanced by Combination with Existing Anticancer Therapies: Turn up the Heat!Journal of Cancer · 2025Review
- Editorial: Deciphering cell-cell interactions in triple-negative breast cancer.Frontiers in immunology · 2025Article
- Adenosine receptors on the immuno-oncology expressway: TIME, perspectives, and translation.Frontiers in immunology · 2025Review
- CD73: a new immune checkpoint for leukemia treatment.Frontiers in immunology · 2025Review
- TRIM21: a multifaceted regulator in cancer.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
21 authors at 6 institutions in 1 country.
Funding
Abstract
Despite widespread utilization of immunotherapy, treating immune-cold tumors remains a challenge. Multiomic analyses and experimental validation identified the OTUD4/CD73 proteolytic axis as a promising target in treating immune-suppressive triple negative breast cancer (TNBC). Mechanistically, deubiquitylation of CD73 by OTUD4 counteracted its ubiquitylation by TRIM21, resulting in CD73 stabilization inhibiting tumor immune responses. We further demonstrated the importance of TGF-β signaling for orchestrating the OTUD4/CD73 proteolytic axis within tumor cells. Spatial transcriptomics profiling discovered spatially resolved features of interacting malignant and immune cells pertaining to expression levels of OTUD4 and CD73. In addition, ST80, a newly developed inhibitor, specifically disrupted proteolytic interaction between CD73 and OTUD4, leading to reinvigoration of cytotoxic CD8+ T cell activities. In preclinical models of TNBC, ST80 treatment sensitized refractory tumors to anti-PD-L1 therapy. Collectively, our findings uncover what we believe to be a novel strategy for targeting the immunosuppressive OTUD4/CD73 proteolytic axis in treating immune-suppressive breast cancers with the inhibitor ST80.
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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.