ArticleFrontiers in immunology2022
Over-Expression of GUSB Leads to Primary Resistance of Anti-PD1 Therapy in Hepatocellular Carcinoma.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Current status and challenges of immune checkpoint inhibitors in liver cancer: from monotherapy to combination strategies.Medical oncology (Northwood, London, England) · 2026Review
- The Evolving Landscape of Hepatocellular Carcinoma Therapy: From Conventional Modalities to TME-Responsive Prodrug Design Strategies.Drug design, development and therapy · 2026Review
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- Analysis of genomic ancestry and characterization of a new variant in MPS type VII.Orphanet journal of rare diseases · 2025Article
- Article
- Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis.iScience · 2024Article
- ARHGAP18 is Upregulated by Transcription Factor GATA1 Promotes the Proliferation and Invasion in Hepatocellular Carcinoma.Applied biochemistry and biotechnology · 2024Article
- Clinical Significance of Non-Coding RNA Regulation of Programmed Cell Death in Hepatocellular Carcinoma.Cancers · 2023Review
- LncASAP1-IT1 promotes hepatocellular carcinoma progression through the regulation of the miR-1294/TGFBR1 pathwayJournal of gastrointestinal oncology · 2023Article
- Genetics of enzymatic dysfunctions in metabolic disorders and cancer.Frontiers in oncology · 2023Review
- Noncoding RNAs as an emerging resistance mechanism to immunotherapies in cancer: basic evidence and therapeutic implications.Frontiers in immunology · 2023Review
- Case report: Predictability of clinical response and rejection risk after immune checkpoint inhibition in liver transplantation.Frontiers in transplantation · 2023Article
- The current status and future of PD-L1 in liver cancer.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapy treatments, particularly immune checkpoint blockade, can result in benefits in clinical settings. But many pre-clinical and clinical studies have shown that resistance to anti-PD1 therapy frequently occurs, leading to tumor recurrence and treatment failure, including in patients with hepatocellular carcinoma (HCC). In this study, 10 patients with HCC were remedied with anti-PD1, and pre-treatment biopsy samples were sequenced for 289 nanostring panel RNA to compare responsive and non-responsive tumors to identify possible pretreatment biomarkers or targets of anti-PD1 therapeutic responses. Fortunately, the expression of β-Glucuronidase (GUSB) in the non-responding tumors was found to be remarkably higher than that in responding tumors. Results of the cell counting kit 8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell, wound healing test, and flow cytometry showed that GUSB facilitated proliferation, invasion, as well as migration of human HCC cells and downregulated PD-L1 expression by promoting miR-513a-5p. Additionally, as a GUSB inhibitor, amoxapine can reduce the progression of human HCC cells, and was an effective treatment for HCC and improved the sensitivity of anti-PD1 therapy. In summary, this study reveals that increased GUSB downregulates PD-L1 expression by promoting miR-513a-5p, leading to primary resistance to anti-PD1 treatment in HCC, and amoxapine enhances the sensitivity of anti-PD1 therapy by inhibiting GUSB, providing a new strategy and method for improving the efficacy of anti-PD1 therapy and bringing new prospects for therapy of HCC.
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