Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels
Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels
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DOI：
10.1016/j.bbmt.2007.12.490
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发表时间：
2008-03-01
影响因子：
4.3
通讯作者：
Hakint, Frances T.
中科院分区：
文献类型：
--
作者：
Boyiadzis, Michael;Memon, Sarfraz;Hakint, Frances T.
由于自然杀伤（NK）细胞可以在异基因造血干细胞移植后有效的抗肿瘤效应，我们研究了异基因造血干细胞移植患者的NK重建和受体表达，重点是激活受体，触发抗肿瘤反应。我们确定，NK水平在围移植期是成反比的NK稳态细胞因子IL-15的血浆水平的急剧上升和下降，这增加了50倍以上，从预处理到移植的一天，在淋巴细胞减少的准备方案。此外，在与IL-15一起培养的NK细胞中，我们观察到激活受体NKG 2D、NKp 30和NKp 46的上调，与抗肿瘤Lyric活性的增加相关。类似地，这些活化受体的表达在移植后早期显著增加，同时总NK细胞迅速增加，并向CD 56表达增加的方向转变。这些数据表明，移植物的细胞因子环境，特别是升高的IL-15水平，可能通过增强NK亚群的恢复和调节活化受体的表达而有助于移植后的抗肿瘤功效。(C)2008年美国血液和骨髓移植协会。
Because natural killer (NK) cells can be potent anti-tumor effectors after allogeneic stem cell transplantation, we investigated NK reconstitution and receptor expression in patients undergoing allogeneic hematopoietic stem cell transplantation, focusing on the activating receptors that trigger anti-tumor responses. We determined that NK levels in the peri-transplant period were inversely proportional to the dramatic rise and fall in plasma levels of the NK homeostatic cytokine IL-15, which increased more than 50-fold from pretreatment to the day of transplant during the lymphoreductive preparative regimen. Furthermore, in NK cells cultured with IL-15, we observed an up-regulation of the activating receptors NKG2D, NKp30, and NKp46, associated with an increase in anti-tumor lyric activity. Similarly, the expression of these activating receptors increased significantly during the early post-transplant period, concurrent with a rapid increase in total NK cells and a shift toward increased expression of CD56. These data suggest that the cytokine milieu of transplants, in particular elevated levels of IL-15, may contribute to anti-tumor efficacy post-transplant by enhancing the recovery of NK subsets and modulating expression of activating receptors. (C) 2008 American Society for Blood and Marrow Transplantation.