ArticleThe Journal of clinical investigation2023
CRISPR screening identifies the deubiquitylase ATXN3 as a PD-L1-positive regulator for tumor immune evasion.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Ubiquitin-driven regulation of immune checkpoints in lung cancer: Mechanisms and therapeutic implications (Review).Experimental and therapeutic medicine · 2026Review
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Loss of NCCRP1 overcomes immune evasion in lung adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- Expression of PIEZO1 in lung adenocarcinoma correlates with PD-L1 expression, cell migration, and poor prognosis: an exploratory study.Discover oncology · 2026Article
- Emerging CRISPR Approaches for Countering Immune Evasion: Insight from Recent Studies.International journal of molecular sciences · 2026Review
- Hypoxia promotes progression of cervical cancer by modulating the ATXN3-enhanced P53 stability or STAT5 phosphorylation.Cell death discovery · 2026Article
- Mechanism of Yiqi Huoxue Granule in promoting angiogenesis of skin lesion tissue by increasing CSF2 to reduce mesenchymal stem cell apoptosis.Frontiers in pharmacology · 2026Article
- Spatiotemporal control of mitoribosome-mediated metabolic reprogramming in cancer: implications for heterogeneity and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Galectins at the crossroads of tumor immunity, metabolism, and metastasis: mechanisms, therapeutic resistance, and translational opportunities.Frontiers in immunology · 2026Review
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- Gene editing for Spinocerebellar ataxia type 3 taking advantage of the human ATXN3L paralog as replacement gene.Gene therapy · 2025Article
- JUNB and JUND in Urological Cancers: A Literature Review.Current issues in molecular biology · 2025Review
- Molecular characterization underlying IFN-α2 treatment in polycythemia vera: a transcriptomic overview.Molecular and cellular biochemistry · 2025Article
- Succinate drives gut inflammation by promoting FOXP3 degradation through a molecular switch.Nature immunology · 2025Article
- Finding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies.Oncogene · 2025Review
- Predicting Which Mitophagy Proteins Are Dysregulated in Spinocerebellar Ataxia Type 3 (SCA3) Using the Auto-p2docking Pipeline.International journal of molecular sciences · 2025Article
- The deubiquitinating enzyme ATXN3 promotes hepatocellular carcinoma progression by stabilizing TAZ.Cancer gene therapy · 2025Article
- Distinct strategies for intravascular triglyceride metabolism in hearts of mammals and lower vertebrate species.JCI insight · 2024Article
- ATXN3 functions as a tumor suppressor through potentiating galectin-9-mediated apoptosis in human colon adenocarcinoma.The Journal of biological chemistry · 2024Article
- Protein O-fucosyltransferase 1 promotes PD-L1 stability to drive immune evasion and directs liver cancer to immunotherapy.Journal for immunotherapy of cancer · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Regulation of tumoral PD-L1 expression is critical to advancing our understanding of tumor immune evasion and the improvement of existing antitumor immunotherapies. Herein, we describe a CRISPR-based screening platform and identified ATXN3 as a positive regulator for PD-L1 transcription. TCGA database analysis revealed a positive correlation between ATXN3 and CD274 in more than 80% of human cancers. ATXN3-induced Pd-l1 transcription was promoted by tumor microenvironmental factors, including the inflammatory cytokine IFN-γ and hypoxia, through protection of their downstream transcription factors IRF1, STAT3, and HIF-2α. Moreover, ATXN3 functioned as a deubiquitinase of the AP-1 transcription factor JunB, indicating that ATNX3 promotes PD-L1 expression through multiple pathways. Targeted deletion of ATXN3 in cancer cells largely abolished IFN-γ- and hypoxia-induced PD-L1 expression and consequently enhanced antitumor immunity in mice, and these effects were partially reversed by PD-L1 reconstitution. Furthermore, tumoral ATXN3 suppression improved the preclinical efficacy of checkpoint blockade antitumor immunotherapy. Importantly, ATXN3 expression was increased in human lung adenocarcinoma and melanoma, and its levels were positively correlated with PD-L1 as well as its transcription factors IRF1 and HIF-2α. Collectively, our study identifies what we believe to be a previously unknown deubiquitinase, ATXN3, as a positive regulator for PD-L1 transcription and provides a rationale for targeting ATXN3 to sensitize checkpoint blockade antitumor immunotherapy.
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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.