A VEGFR-3 Antagonist Increases IFN-gamma Expression on Low Functioning NK Cells in Acute Myeloid Leukemia

作者：Lee Ji Yoon; Park Sohye; Kim Donghyun Curt; Yoon Jae Ho; Shin Seung Hwan; Min Woo Sung; Kim Hee Je^*

来源：Journal of Clinical Immunology, 2013, 33(4): 826-837.

DOI：10.1007/s10875-013-9877-2

• VEGFR-3
• acute myeloid leukemia
• natural killer cells
• interferon-gamma
• antagonist

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)-gamma, 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-gamma in NK cells. %26lt;br%26gt;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. %26lt;br%26gt;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-gamma. VEGFR-3-expressing AML NK cells were less potent than healthy NK cells in terms of killing K562 cells. The level of IFN-gamma in AML NK cells was increased by VEGFR-3 antagonist treatment, indicating the functional relevance of VEGFR-3 in IFN-gamma-secreting NK cells. %26lt;br%26gt;Conclusion Collectively, our data suggest a relationship between VEGFR-3 and IFN-gamma 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.

• 出版日期2013-5