ArticleCell stem cell2024
Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells.
Article in Cell stem cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- Mechanism of Coumarin in the anti-liver cancer activity by promoting NK cell activation.Medical oncology (Northwood, London, England) · 2026Article
- Trained immunity: New insights into pathogenesis and therapeutic targets in diabetes and diabetic complications.Genes & diseases · 2026Review
- Integrated Transcriptomic Analyses Identify Four Prognosis-Associated Genes in Hepatocellular Carcinoma.International journal of molecular sciences · 2026Article
- Triple-Negative Breast Cancer Cells Utilize IL8 and CXCL1 to Suppress NK Cells' Function and Facilitate Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- Nur77 agonism invigorates Natural Killer cell immunity against hepatocellular carcinoma.Nature communications · 2026Article
- Derivation of functional early gestation decidual natural killer cell subtypes from induced pluripotent stem cells.Stem cells (Dayton, Ohio) · 2026Article
- Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026Review
- Improved expansion of peripheral blood and iPSC-derived natural killer cells for clinical applications.Cell reports methods · 2026Article
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Osteopontin-driven TGF-β1 signaling via integrin αvβ3-NF-κB axis impairs NK cell function in head and neck squamous cell carcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Transcriptional Profile Change of NK-92 Cells in Presence of Cytokines, TGFβ Signaling Pathway Inhibitor and CDK7/12/13 Kinase Inhibitor.International journal of molecular sciences · 2026Article
- TGFβ1 Activates Lnc-APUE to Promote Tumor Metastasis via the Alu Element-Driven STAU1-Mediated Decay of CDH1 mRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TriCON: A Carbon-Based Triple-Modal Nanoplatform for Pancreatic Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Improving surgical treatments for hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2026Review
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β.Cell death discovery · 2026Article
- Obstacles and improvement strategies for CAR-T cell therapy in solid tumors.Discover oncology · 2026Review
- Human pluripotent stem cell-derived innate and adaptive immune cells for cancer immunotherapy.Cell stem cell · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Transforming growth factor beta (TGF-β) is highly expressed in the liver tumor microenvironment and is known to inhibit immune cell activity. Here, we used human induced pluripotent stem cells (iPSCs) to produce natural killer (NK) cells engineered to mediate improved anti-HCC activity. Specifically, we produced iPSC-NK cells with either knockout TGF-β receptor 2 (TGFBR2-KO) or expression of a dominant negative (DN) form of the TGF-β receptor 2 (TGFBR2-DN) combined with chimeric antigen receptors (CARs) that target either GPC3 or AFP. The TGFBR2-KO and TGFBR2-DN iPSC-NK cells are resistant to TGF-β inhibition and improved anti-HCC activity. However, expression of anti-HCC CARs on iPSC-NK cells did not lead to effective anti-HCC activity unless there was also inhibition of TGF-β activity. Our findings demonstrate that TGF-β signaling blockade is required for effective NK cell function against HCC and potentially other malignancies that express high levels of TGF-β.
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