Enhanced cytotoxic activity of ex vivo-differentiated human natural killer cells in the presence of HOXB4
Autor: | Gianfranco Pittari, Arash Nanbakhsh, Ania Tejchman, Cécile Pochon, Jean Bourhis, Sophie Amsellem, Salem Chouaib |
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Přispěvatelé: | Institut Gustave Roussy (IGR), Hématologie - Greffe de moelle, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Department of medical oncology, Hamad medical corporation, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
Rok vydání: | 2014 |
Předmět: |
Cytotoxicity
Immunologic Cancer Research [SDV]Life Sciences [q-bio] Antigens CD34 Granzymes Interleukin 21 MESH: Up-Regulation Immunology and Allergy Cytotoxic T cell Transgenes biology Janus kinase 3 Degranulation Cell Differentiation MESH: Antigens CD56 MESH: Transcription Factors Fetal Blood CD56 Antigen Cell biology Up-Regulation Killer Cells Natural Interleukin 12 MESH: Killer Cells Natural MESH: Cell Differentiation Immunology MESH: Transgenes MESH: Coculture Techniques MESH: Gene Expression Profiling MESH: Homeodomain Proteins Humans MESH: Fetal Blood MESH: Cytotoxicity Immunologic Pharmacology MESH: Granzymes Homeodomain Proteins MESH: K562 Cells Lymphokine-activated killer cell MESH: Humans Gene Expression Profiling MESH: Antigens CD34 Microarray Analysis Coculture Techniques Granzyme B MESH: Microarray Analysis Granzyme biology.protein MESH: Stromal Cells Stromal Cells K562 Cells Transcription Factors |
Zdroj: | Journal of Immunotherapy Journal of Immunotherapy, Lippincott, Williams & Wilkins, 2014, 37 (5), pp.278-282 |
ISSN: | 1537-4513 1524-9557 |
Popis: | International audience; We have previously shown that human umbilical cord blood CD34 progenitor cells undergo in vitro differentiation into functional natural killer (NK) cells and that their coculture in the presence of HOXB4-transduced stromal MS-5 cells resulted in an increase in differentiated NK number. The present study was conducted to compare the stromal effect on NK lytic potential in the presence and absence of HOXB4. Our results provide evidence that HOXB4-transduced MS-5 cells as compared with transduced GFP (+) MS-5 cells induced highly differentiated cytotoxic NK cells. Importantly, this difference was not because of the expression of activating NK receptors but was associated with an increased induction of granzyme B degranulation in response to stimulation with NK cell susceptible targets. DNA microarray-based global transcriptional profiling confirmed the upregulation of granzyme B. These findings provide further evidence that HOXB4 is a crucial regulator of NK function and that its use in generating functional NK cells with increased lytic potential may be significant for cancer immunotherapy. |
Databáze: | OpenAIRE |
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