Oncotarget

Research Papers:

The anti-tumor role of NK cells in vivo pre-activated and re-stimulated by interleukins in acute lymphoblastic leukemia

Fengyan Jin, Hai Lin, Sujun Gao, Zheng Hu, Song Zuo, Liguang Sun, Chunhui Jin, Wei Li and Yanping Yang _

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Oncotarget. 2016; 7:79187-79202. https://doi.org/10.18632/oncotarget.13007

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Abstract

Fengyan Jin1, Hai Lin1, Sujun Gao1, Zheng Hu2, Song Zuo2, Liguang Sun2, Chunhui Jin1, Wei Li1, Yanping Yang1

1Department of Hematology, The First Bethune Hospital of Jilin University, Changchun, China

2Institute of Translational Medicine, The First Bethune Hospital of Jilin University, Changchun, China

Correspondence to:

Yanping Yang, email: yangyanping_1978@163.com

Keywords: natural killer cells, interleukin, interferon-γ, NKG2D, leukemia

Received: December 13, 2015     Accepted: October 26, 2016     Published: November 01, 2016

ABSTRACT

Although natural killer cells (NK cells) were traditionally classified as members of the innate immune system, NK cells have recently been found also to be an important player in the adaptive immune systems. In this context, in vitro activation of NK cells by cytokines leads to generation of NK cells with memory-like properties characterized by increased interferon-γ (IFNγ) production. However, it remains to be defined whether these memory-like NK cells exist in vivo after cytokine activation. Furthermore, it is also unclear whether such memory-like NK cells induced in vivo by cytokines could have effective anti-leukemia response. To address these issues, we used an in vivo pre-activation and re-stimulation system that was able to produce NK cells with increased IFNγ secretion. It was found that after in vivo pre-activation and re-stimulation with interleukins (ILs), NK cells retained a state to produce increased amount of IFNγ. Of note, whereas this intrinsic capacity of enhanced IFNγ production after in vivo IL pre-activation and re-stimulation could be transferred to the next generation of NK cells and was associated with prolonged survival of the mice with acute lymphoid leukemia. Moreover, the anti-leukemia activity of these memory-like NK cells was associated with IFNγ production and up-regulation of NK cells activation receptor-NK Group 2 member D (NKG2D). Together, these findings argue strongly that in vivo IL pre-activation and re-stimulation is capable to induce memory-like NK cells as observed previously in vitro, which are effective against acute lymphoblastic leukemia, likely via NKG2D-dependent IFNγ production, in intact animals.


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