ArticleCancer immunology, immunotherapy : CII2018
An IL-15 superagonist/IL-15Rα fusion complex protects and rescues NK cell-cytotoxic function from TGF-β1-mediated immunosuppression.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- The quadruple immunotherapy for colorectal cancer (QuICC) trial for mismatch repair-proficient metastatic colorectal cancer.The oncologist · 2026Trial
- Quick efficacy seeking trial (QuEST1): a novel combination immunotherapy study designed for rapid clinical signal assessment metastatic castration-resistant prostate cancer.Journal for immunotherapy of cancer · 2018Trial
- Armed Oncolytic Myxoma Virus Induces Systemic Antitumor Immunity Against Solid Tumors in Immunocompetent Mice.Research square · 2026Article
- CD155 and its receptors in glioma: prospects for emerging immune checkpoint inhibitors.Acta neuropathologica communications · 2026Review
- The PVR-TIGIT/CD96/CD226 axis: a novel immune checkpoint target in ovarian cancer.Frontiers in immunology · 2026Review
- Immunotherapeutic strategies targeting the PVR-TIGIT/CD96/CD226 signaling pathway in glioma treatment.Annals of medicine · 2025Review
- Structure and function of therapeutic antibodies approved by the US FDA in 2024.Antibody therapeutics · 2025Review
- Identification of natural killer cell-characteristic genes in atherosclerosis based on bioinformatics analysis.Scientific reports · 2025Article
- TGF-β-driven NK Cells plasticity in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- Enhancing Therapeutic Efficacy of FLT3 Inhibitors with Combination Therapy for Treatment of Acute Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Machine learning identifies the role of SMAD6 in the prognosis and drug susceptibility in bladder cancer.Journal of cancer research and clinical oncology · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Combined therapy of CAR-IL-15/IL-15Rα-T cells and GLIPR1 knockdown in cancer cells enhanced anti-tumor effect against gastric cancer.Journal of translational medicine · 2024Article
- Natural killer cells for pancreatic cancer immunotherapy: Role of nanoparticles.Cancer letters · 2023Article
- Advanced T and Natural Killer Cell Therapy for Glioblastoma.Journal of Korean Neurosurgical Society · 2023Article
- Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies.Cells · 2023Review
- Functional crosstalk and regulation of natural killer cells in tumor microenvironment: Significance and potential therapeutic strategies.Genes & diseases · 2023Review
- Review
- Adoptive NK Cell Therapy - a Beacon of Hope in Multiple Myeloma Treatment.Frontiers in oncology · 2023Review
- Skin infiltrating NK cells in cutaneous T-cell lymphoma are increased in number and display phenotypic alterations partially driven by the tumor.Frontiers in immunology · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Natural killer (NK) cells are innate cytotoxic lymphocytes that play a fundamental role in the immunosurveillance of cancers. NK cells of cancer patients exhibit impaired function mediated by immunosuppressive factors released from the tumor microenvironment (TME), such as transforming growth factor (TGF)-β1. An interleukin (IL)-15 superagonist/IL-15 receptor α fusion complex (IL-15SA/IL-15RA; ALT-803) activates the IL-15 receptor on CD8 T cells and NK cells, and has shown significant anti-tumor activity in several in vivo studies. This in vitro study investigated the efficacy of IL-15SA/IL-15RA on TGF-β1-induced suppression of NK cell-cytotoxic function. IL-15SA/IL-15RA inhibited TGF-β1 from decreasing NK cell lysis of four of four tumor cell lines (H460, LNCap, MCF7, MDA-MB-231). IL-15SA/IL-15RA rescued healthy donor and cancer patient NK cell-cytotoxicity, which had previously been suppressed by culture with TGF-β1. TGF-β1 downregulated expression of NK cell-activating markers and cytotoxic granules, such as CD226, NKG2D, NKp30, granzyme B, and perforin. Smad2/3 signaling was responsible for this TGF-β1-induced downregulation of NK cell-activating markers and cytotoxic granules. IL-15SA/IL-15RA blocked Smad2/3-induced transcription, resulting in the rescue of NK cell-cytotoxic function from TGF-β1-induced suppression. These findings suggest that in addition to increasing NK cell function via promoting the IL-15 signaling pathway, IL-15SA/IL-15RA can function as an inhibitor of TGF-β1 signaling, providing a potential remedy for NK cell dysfunction in the immunosuppressive tumor microenvironment.
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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.