ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Targeting Lin28 axis enhances glypican-3-CAR T cell efficacy against hepatic tumor initiating cell population.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Emerging Immune-Based Therapeutic Strategies in Hepatocellular Carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Spatiotemporal heterogeneity of neutrophil extracellular traps in hepatocellular carcinoma microenvironment and targeted therapy progress.Journal of translational medicine · 2026Review
- Targeting the Lin28/let-7 Axis with Compounds to Regulate Transcriptional Control in Cancer.Anti-cancer agents in medicinal chemistry · 2026Review
- STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities.Frontiers in immunology · 2026Review
- Inhibition of RNA-binding proteins enhances immunotherapy in ovarian cancer.Signal transduction and targeted therapy · 2025Article
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- The regulatory roles of RNA-binding proteins in the tumour immune microenvironment of gastrointestinal malignancies.RNA biology · 2025Review
- Targeting Glypican-3 for Liver Cancer Therapy: Clinical Applications and Detection Methods.Journal of clinical and translational hepatology · 2025Review
- Aquaglyceroporin-7 ameliorates sorafenib resistance and immune evasion in hepatocellular carcinoma through inhibition of lipid accumulation.Cellular and molecular life sciences : CMLS · 2025Article
- The role of RNA binding proteins in cancer biology: A focus on FMRP.Genes & diseases · 2025Review
- IL-21 Loading CaMnCOSmall (Weinheim an der Bergstrasse, Germany) · 2025Article
- Multifaceted roles of OCT4 in tumor microenvironment: biology and therapeutic implications.Oncogene · 2025Review
- Role of Kynurenine and Its Derivatives in Liver Diseases: Recent Advances and Future Clinical Perspectives.International journal of molecular sciences · 2025Review
- LIN28B promotes the progression of endometrial cancer through upregulating MYC and correlates with immune microenvironment.Frontiers in oncology · 2025Article
- Precision immunotherapy with CAR-T cells in pediatric B-cell acute lymphoblastic leukemia: advances and unanswered challenges.Frontiers in oncology · 2025Review
- The impact of metabolic reprogramming in hepatocellular carcinoma on T cell.Frontiers in immunology · 2025Review
- Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.Journal of hematology & oncology · 2024Review
- GPC3-mediated metabolic rewiring of diabetic mesenchymal stromal cells enhances their cardioprotective functions via PKM2 activation.iScience · 2024Article
- Ubiquitination-specific protease 7 enhances stemness of hepatocellular carcinoma by stabilizing basic transcription factor 3.Functional & integrative genomics · 2024Article
- LIN28 upregulation in primary human T cells impaired CAR T antitumoral activity.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Overexpression of Lin28 is detected in various cancers with involvement in the self-renewal process and cancer stem cell generation. In the present study, we evaluated how the Lin28 axis plays an immune-protective role for tumor-initiating cancer cells in hepatocellular carcinoma (HCC). Our result using HCC patient samples showed a positive correlation between indoleamine 2,3-dioxygenase-1 (IDO1), a kynurenine-producing enzyme with effects on tumor immune escape, and Lin28B. Using in silico prediction, we identified a Sox2/Oct4 transcriptional motif acting as an enhancer for IDO1. Knockdown of Lin28B reduced Sox2/Oct4 and downregulated IDO1 in tumor-initiating hepatic cancer cells. We further observed that inhibition of Lin28 by a small-molecule inhibitor (C1632) suppressed IDO1 expression. Suppression of IDO1 resulted in a decline in kynurenine production from tumor-initiating cells. Inhibition of the Lin28 axis also impaired PD-L1 expression in HCC cells. Consequently, modulating Lin28B enhanced in vitro cytotoxicity of glypican-3 (GPC3)-chimeric antigen receptor (CAR) T and NK cells. Next, we observed that GPC3-CAR T cell treatment together with C1632 in a HCC xenograft mouse model led to enhanced anti-tumor activity. In conclusion, our results suggest that inhibition of Lin28B reduces IDO1 and PD-L1 expression and enhances immunotherapeutic potential of GPC3-CART cells against HCC.
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