ArticleCell death and differentiation2023
Targeting ubiquitin-specific protease 8 sensitizes anti-programmed death-ligand 1 immunotherapy of pancreatic cancer.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Efficacy hierarchy and absolute survival benefit of first-line immunotherapy in advanced gastric cancer: a meta-analysis and pooled survival analysis.Frontiers in immunology · 2026Pooled it
- Article
- Post-Translational Modifications in Pancreatic Cancer: Mechanisms to Clinical Applications.Journal of gastroenterology and hepatology · 2026Review
- BRCC3 promotes progression and immune evasion in non-small cell lung cancer through regulation of PD-L1 and B7-H3.Journal of molecular histology · 2026Article
- Phosphorylation-dependent STAMBP drives the progression of pancreatic ductal adenocarcinoma by deubiquitinating and stabilizing BAG3.Cell death and differentiation · 2026Article
- USP21 drives immune evasion in colorectal cancer via deubiquitination and stabilization of β-catenin.Cellular & molecular immunology · 2026Article
- UBA6 serves as a prognostic biomarker and promotes tumor progression in pancreatic ductal adenocarcinoma.Translational cancer research · 2026Article
- Targeting PSMD14 enhances immunotherapy efficacy by promoting PD-L1 degradation and reshaping the tumor microenvironment in breast cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Influence of USP15 and its derived-peptide on non-small cell lung cancer immune evasion via regulating PD-L1 stability.Journal for immunotherapy of cancer · 2026Article
- Deubiquitinase USP8 regulates the spindle assembly checkpoint in oocytes.Science advances · 2026Article
- USP10 regulates HIF2α stability by deubiquitinating HIF2α regardless ofTranslational andrology and urology · 2026Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- Review
- Molecular Mechanisms of the Ubiquitin-Specific Proteases (USPs) Family in Biliary Tract Cancer and Targeted Intervention Strategies.Biomedicines · 2025Review
- The multifaceted roles of deubiquitinating enzymes (DUBs) in pancreatic ductal adenocarcinoma.Cell death & disease · 2025Review
- Article
- Intermediate Conductance Calcium-Dependent Potassium Channel (KJournal of cellular physiology · 2025Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) help tumor cells evade immune surveillance, and are regarded as important targets of anti-tumor immunotherapy. Post-translational modification of PD-L1 has potential value in immunosuppression. Here, we identified that ubiquitin-specific protease 8 (USP8) deubiquitinates PD-L1. Pancreatic cancer tissues exhibited significantly increased USP8 levels compared with those in normal tissues. Clinically, the expression of USP8 showed a significant association with the tumor-node-metastasis stage in multiple patient-derived cohorts of pancreatic cancer. Meanwhile, USP8 deficiency could reduce tumor invasion and migration and tumor size in an immunity-dependent manner, and improve anti-tumor immunogenicity. USP8 inhibitor pretreatment led to reduced tumorigenesis and immunocompetent mice with Usp8 knockdown tumors exhibited extended survival. Moreover, USP8 interacted positively with PD-L1 and upregulated its expression by inhibiting the ubiquitination-regulated proteasome degradation pathway in pancreatic cancer. Combination therapy with a USP8 inhibitor and anti-PD-L1 effectively suppressed pancreatic tumor growth by activation of cytotoxic T-cells and the anti-tumor immunity was mainly dependent on the PD-L1 pathway and CD8 + T cells. Our findings highlight the importance of targeting USP8, which can sensitize PD-L1-targeted pancreatic cancer to immunotherapy and might represent a novel therapeutic strategy to treat patients with pancreatic tumors in the future.
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