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Activation of the FcgammaReceptorIIIa on human natural killer cells leads to increased expression of functional interleukin-21 receptor.
- Source :
-
OncoImmunology . 2017, Vol. 6 Issue 5, pN.PAG-N.PAG. 1p. - Publication Year :
- 2017
-
Abstract
- Natural killer (NK) cells are innate immune effector cells that play a crucial role in immune surveillance and the destruction of cancer cells. NK cells express a low-affinity receptor for the Fc or constant region of immunoglobulin G (FcγRIIIa) and multiple cytokine receptors that respond to antibody-coated targets and cytokines in the tumor microenvironment. In the present work, microarray gene expression analysis revealed that the IL-21 receptor (IL-21R) was strongly upregulated following FcR stimulation. The IL-21R was found to be upregulated on FcR-stimulated NK cells at the transcript level as determined by reverse transcription polymerase chain reaction (RT-PCR). Immunoblot analysis revealed that protein expression of the IL-21R peaked at 8 h post-stimulation of the FcR. Inhibition of the mitogen-activated protein kinase (MAPK) pathway downstream of the FcR blocked the induction of IL-21R expression. Increased expression of the IL-21R sensitized NK cells to IL-21 stimulation, as treatment of FcR-stimulated NK cells led to significantly increased phosphorylation of STAT1 and STAT3, as measured by intracellular flow cytometry and immunoblot analysis. Following FcR-stimulation, IL-21-activated NK cells were better able to mediate the lysis of trastuzumab-coated human epidermal growth factor receptor 2 (HER2+) SK-BR-3 tumor cells as compared to control-treated cells. Likewise, IL-21-induced NK cell secretion of IFNγ following exposure to antibody-coated tumor cells was enhanced following FcR-stimulation. The analysis of NK cells from patients receiving trastuzumab therapy for HER2+cancer exhibited increased levels of the IL-21R following the administration of antibody suggesting that the presence of monoclonal antibody-coated tumor cellsin vivocan stimulate the increased expression of IL-21R on NK cells. [ABSTRACT FROM PUBLISHER]
- Subjects :
- *KILLER cells
*IMMUNOGLOBULIN G
*CYTOKINE receptors
*GENE expression
*INTERLEUKIN-21
Subjects
Details
- Language :
- English
- ISSN :
- 21624011
- Volume :
- 6
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- 123479392
- Full Text :
- https://doi.org/10.1080/2162402X.2017.1312045