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
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