Abstract
The stimulatory natural killer group 2 member D (NKG2D) lymphocyte receptor, initially discovered and expressed mostly on natural killer (NK) cells, T cells and natural killer T cells, can promote tumor immune surveillance. However, with increasing tumor grade, tumors themselves express NKG2D to self-stimulate oncogenic pathways. To confirm that cancer cells themselves express NKG2D, we have now investigated the role of the tumoral NKG2D in NK cell-mediated immune surveillance. Both anti-NKG2D and shRNA to that down-regulated tumoral NKG2D increased the number of cells in G1 phase and S phase, increased the expression of cyclin E–CDK2 and decreased P21. In addition, CD107a, IFN-γ and TNF-α increased when the cells were treated with anti-NKG2D which suggests that blocking tumoral NKG2D could augment tumor surveillance of NK cells. Altogether, tumoral NKG2D stimulates cell propagation and immune escape in acute myeloid leukemia cells.
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Acknowledgments
This project was supported by the National Natural Science Foundation of China (NSFC81473125), Specialized Research Fund for the Doctoral Program of Higher Education (20130096110007), Jiangsu Province Qinglan Project (2014) and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. We are grateful to Professor Sherie L. Morrison of University of California Los Angeles for her revision on this article.
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Mingying Tang and Desmond Omane Acheampong have contributed equally to this work.
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Tang, M., Acheampong, D.O., Wang, Y. et al. Tumoral NKG2D alters cell cycle of acute myeloid leukemic cells and reduces NK cell-mediated immune surveillance. Immunol Res 64, 754–764 (2016). https://doi.org/10.1007/s12026-015-8769-3
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DOI: https://doi.org/10.1007/s12026-015-8769-3