ArticleScientific reports2016
IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
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- Advances in understanding the role of immune checkpoint LAG-3 in tumor immunity: a comprehensive review.Frontiers in oncology · 2024Review
- The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes.Frontiers in immunology · 2022Review
- WASF2 Serves as a Potential Biomarker and Therapeutic Target in Ovarian Cancer: A Pan-Cancer Analysis.Frontiers in oncology · 2022Article
- Inhibitory Receptors and Immune Checkpoints Regulating Natural Killer Cell Responses to Cancer.Cancers · 2021Review
- CRISPR-Cas9-Mediated TIM3 Knockout in Human Natural Killer Cells Enhances Growth Inhibitory Effects on Human Glioma Cells.International journal of molecular sciences · 2021Article
- Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells.JCI insight · 2021Article
- Biomechanics of T Cell Dysfunctions in Chronic Diseases.Frontiers in immunology · 2021Review
- The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function.Frontiers in cell and developmental biology · 2021Review
- The Next-Generation Immune Checkpoint LAG-3 and Its Therapeutic Potential in Oncology: Third Time's a Charm.International journal of molecular sciences · 2020Review
- Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse.Frontiers in immunology · 2020Review
- Unleashing Natural Killer Cells in the Tumor Microenvironment-The Next Generation of Immunotherapy?Frontiers in immunology · 2020Review
- NK Cell-Based Immune Checkpoint Inhibition.Frontiers in immunology · 2020Review
- Activation of compensatory pathways via Rac2 in the absence of the Cdc42 effector Wiskott-Aldrich syndrome protein in Dendritic cells.Small GTPases · 2019Article
- The Common Cytokine Receptor γ Chain Family of Cytokines.Cold Spring Harbor perspectives in biology · 2018Review
- The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy.Genes & cancer · 2018Review
- IL-2 mediates NK cell proliferation but not hyperactivity.Immunologic research · 2018Article
- Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
To kill target cells, natural killer (NK) cells organize signaling from activating and inhibitory receptors to form a lytic synapse. Wiskott-Aldrich syndrome (WAS) patients have loss-of-function mutations in the actin regulator WASp and suffer from immunodeficiency with increased risk to develop lymphoreticular malignancies. NK cells from WAS patients fail to form lytic synapses, however, the functional outcome in vivo remains unknown. Here, we show that WASp KO NK cells had decreased capacity to degranulate and produce IFNγ upon NKp46 stimulation and this was associated with reduced capacity to kill MHC class I-deficient hematopoietic grafts. Pre-treatment of WASp KO NK cells with IL-2 ex vivo restored degranulation, IFNγ production, and killing of MHC class I negative hematopoietic grafts. Moreover, WASp KO mice controlled growth of A20 lymphoma cells that naturally produced IL-2. WASp KO NK cells showed increased expression of DNAM-1, LAG-3, and KLRG1, all receptors associated with cellular exhaustion and NK cell memory. NK cells isolated from WAS patient spleen cells showed increased expression of DNAM-1 and had low to negative expression of CD56, a phenotype associated with NK cells exhaustion. Finally, in a cohort of neuroblastoma patients we identified a strong correlation between WASp, IL-2, and patient survival.
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