Oncotarget

Research Papers:

Programmed differentiated natural killer cells kill leukemia cells by engaging SLAM family receptors

Yang Wu, Young Li, Binqing Fu, Linlin Jin, Xiaohu Zheng, Aimei Zhang, Rui Sun, Zhigang Tian and Haiming Wei _

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Oncotarget. 2017; 8:57024-57038. https://doi.org/10.18632/oncotarget.18659

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Abstract

Yang Wu1, Young Li1, Binqing Fu1,2, Linlin Jin1, Xiaohu Zheng1, Aimei Zhang3, Rui Sun1,2, Zhigang Tian1,2 and Haiming Wei1,2

1Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China

2Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China

3Central Laboratory, Anhui Provincial Hospital, Hefei, China

Correspondence to:

Haiming Wei, email: [email protected]

Zhigang Tian, email: [email protected]

Keywords: natural killer cell, programmed differentiation, leukemia, SLAM family receptors and ligands, therapeutic predictor

Received: March 21, 2017     Accepted: May 23, 2017     Published: June 27, 2017

ABSTRACT

Natural killer (NK) cells are important innate immune cells that can directly kill transformed or virus-infected cells. The adoptive transfer of NK cells has been used to treat hematological malignancies; however, the limited sources and quantities of NK cells have restricted their clinical application. Here, we acquired sufficient quantities of functional NK cells from CD34+ cells treated with a cytokine cocktail. Microarray analysis of the cultured cells revealed a two-stage pattern of programmed differentiation during NK cell development. Different transcription factors were enriched during these two stages, suggesting that preparation of progenitors committed to the NK cell lineage occurs in program 1, while NK cell transformation and maturation occur in program 2. Cultured NK cells highly expressed signaling lymphocytic activation molecule (SLAM) family receptors (SFRs), while leukemia cells expressed SFR ligands. The engagement of these SFRs strengthened the cytotoxicity of NK cells toward leukemia cells. These results demonstrate a simple method of obtaining sufficient NK cells for clinical application, and have categorized NK cell differentiation according to commitment and transformation programs. Moreover, the binding between SFRs on NK cells and their ligands on leukemia cells suggests a new basis for NK cell therapy for treatment of leukemia.


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