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- Title
A VEGFR-3 Antagonist Increases IFN-γ Expression on Low Functioning NK Cells in Acute Myeloid Leukemia.
- Authors
Lee, Ji; Park, Sohye; Kim, Donghyun; Yoon, Jae-Ho; Shin, Seung; Min, Woo-Sung; Kim, Hee-Je
- Abstract
Purpose: Although the importance of vascular endothelial growth factor receptor (VEGFR)-3 has been demonstrated in acute myeloid leukemia (AML), the role of VEGFR-3 in functioning natural killer (NK) cells remains largely unexplored. NK cells can destroy cancer cells by releasing the cytokine interferon (IFN)-γ, but NK cells in AML patients (AML NK cells) have low cytolytic activity. In the present study, we investigated whether lymphatic markers including VEGFR-3 are expressed on low-functioning AML NK cells and VEGFR-3 antagonist can restore expression of IFN-γ in NK cells. Methods: Samples from 67 de novo AML patients and 34 healthy donors were analyzed for lymphatic markers expression using RT-PCR, flow cytometry, and immunostaining. For the cytotoxicity assays, K562 cells and AML NK cells were used as target and effector cells, respectively. To block VEGFR-3, MAZ51 was added to NK cells, which were then subjected to FACS analysis. Results: Compared with NK cells from healthy donors (healthy NK cells), AML NK cells exhibited higher levels of VEGFR-3 and lower expression of IFN-γ. VEGFR-3-expressing AML NK cells were less potent than healthy NK cells in terms of killing K562 cells. The level of IFN-γ in AML NK cells was increased by VEGFR-3 antagonist treatment, indicating the functional relevance of VEGFR-3 in IFN-γ-secreting NK cells. Conclusion: Collectively, our data suggest a relationship between VEGFR-3 and IFN-γ expression in NK cells and raise the possibility of advanced therapeutic approaches involving VEGFR-3 antagonist treatment prior to NK immune cell therapy in AML.
- Subjects
VASCULAR endothelial growth factor receptors; ACUTE myeloid leukemia; KILLER cells; GENE expression; INTERFERONS; CANCER cells; CYTOKINES
- Publication
Journal of Clinical Immunology, 2013, Vol 33, Issue 4, p826
- ISSN
0271-9142
- Publication type
Article
- DOI
10.1007/s10875-013-9877-2