ArticleLeukemia2016
The TGF-β/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- From tumor microenvironment orchestrators to actionable targets: a systematic review of TAM-targeted therapies in triple-negative breast cancer.International journal of clinical oncology · 2026Pooled it
- Trial
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- CAR-NK cell therapy for hematological malignancies.Blood advances · 2026Review
- T-ChroNet: Time-aware chromatin network reconstruction to detect dynamic regulatory programs in longitudinal epigenetic dataset.NAR genomics and bioinformatics · 2026Article
- QBEmax is a sequence-permuted and internally protected base editor.Nature biotechnology · 2026Article
- Expanding Immunotherapy Beyond CAR T Cells: Engineering Diverse Immune Cells to Target Solid Tumors.Cancers · 2025Review
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Rendering NK Cells Antigen-Specific for the Therapy of Solid Tumours.International journal of molecular sciences · 2025Review
- Mendelian randomization analysis reveals the causal relationship between immune cells and leukemia.Discover oncology · 2025Article
- Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies.Cancers · 2025Review
- Improving data interpretability with new differential sample variance gene set tests.BMC bioinformatics · 2025Article
- Transcriptional signature of rapidly responding NK cells reveals S1P5 and CXCR4 as anti-tumor response disruptors.Scientific reports · 2025Article
- Extracellular vesicles in cancer´s communication: messages we can read and how to answer.Molecular cancer · 2025Review
- Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathway.Frontiers in immunology · 2025Article
- CAR-NK cell for gynecological cancers: immune microenvironment remodeling and immunotherapeutic strategies.Frontiers in immunology · 2025Review
- CAR-NK cell therapy: promise and challenges in solid tumors.Frontiers in immunology · 2025Review
- Aclacinomycin enhances the killing effect of allogeneic NK cells on acute myeloid leukemia cells by inducing immunogenic cell death.Frontiers in immunology · 2025Article
- TGF-β Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment.ImmunoTargets and therapy · 2025Article
- Role of transforming growth factor-β1 pathway in angiogenesis induced by chronic stress in colorectal cancer.Cancer biology & therapy · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
Natural killer (NK) cells are key components of the innate immune system, providing potent antitumor immunity. Here, we show that the tumor growth factor-β (TGF-β)/SMAD signaling pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia (ALL). We characterized NK cells in 50 consecutive children with B-ALL at diagnosis, end induction and during maintenance therapy compared with age-matched controls. ALL-NK cells at diagnosis had an inhibitory phenotype associated with impaired function, most notably interferon-γ production and cytotoxicity. By maintenance therapy, these phenotypic and functional abnormalities partially normalized; however, cytotoxicity against autologous blasts remained impaired. We identified ALL-derived TGF-β1 to be an important mediator of leukemia-induced NK cell dysfunction. The TGF-β/SMAD signaling pathway was constitutively activated in ALL-NK cells at diagnosis and end induction when compared with healthy controls and patients during maintenance therapy. Culture of ALL blasts with healthy NK cells induced NK dysfunction and an inhibitory phenotype, mediated by activation of the TGF-β/SMAD signaling pathway, and abrogated by blocking TGF-β. These data indicate that by regulating the TGF-β/SMAD pathway, ALL blasts induce changes in NK cells to evade innate immune surveillance, thus highlighting the importance of developing novel therapies to target this inhibitory pathway and restore antileukemic cytotoxicity.
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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.