Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptors.
Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptors.
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DOI：
10.1007/s00262-009-0724-5
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Boyiadzis M
中科院分区：
文献类型：
--
作者：
Szczepanski MJ;Szajnik M;Welsh A;Foon KA;Whiteside TL;Boyiadzis M
白细胞介素-15（IL-15）在NK细胞稳态中具有主要作用。通过IL-15调节NK细胞受体的相对频率和表达强度可增加癌症患者中NK细胞介导的细胞毒性。我们研究了新诊断的AML患者的受体库并测量了NK细胞活性，并评估了IL-15的体外作用。与健康供体的NK细胞相比，AML患者中活化NK细胞受体的表达显著降低。当从AML患者获得的NK细胞与IL-15一起培养时，与培养前水平相比，活化受体的表达显著上调。同时，NK细胞对自体白血病母细胞的细胞毒活性在IL-15刺激后增加。这种IL-15诱导的活性增加被NK细胞活化受体特异性的中和抗体阻断。这些临床前数据支持未来使用IL-15用于AML患者的基于NK细胞的治疗。
Interleukin-15 (IL-15) has a major role in NK-cell homeostasis. Modulation of the relative frequency and expression intensity of the NK-cell receptors by IL-15 may increase NK cell-mediated cytotoxicity in cancer patients. We investigated the receptor repertoire and measured NK-cell activity in newly diagnosed AML patients and evaluated the ex vivo effects of IL-15. The expression of the activating NK cell receptors was significantly decreased in the AML patients compared to that in NK cells of healthy donors. When NK cells obtained from AML patients were cultured with IL-15, expression of the activating receptors was significantly upregulated compared to pre-culture levels. Concomitantly, cytotoxic activity of NK cells against autologous leukemic blasts increased following IL-15 stimulation. This IL-15 induced increase in activity was blocked by neutralizing antibodies specific for the NK cell activating receptors. These pre-clinical data support the future use of IL-15 for NK cell-based therapies for AML patients.
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影响因子：
4.3
作者：
Boyiadzis, Michael;Memon, Sarfraz;Hakint, Frances T.
通讯作者：
Hakint, Frances T.
影响因子：
20.3
作者：
Nowbakht, P;Ionescu, MCS;Wodnar-Filipowicz, A
通讯作者：
Wodnar-Filipowicz, A
影响因子：
56.9
作者：
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通讯作者：
Spies, T
影响因子：
20.3
作者：
Bryceson, YT;March, ME;Long, EO
通讯作者：
Long, EO
影响因子：
32.4
作者：
Cosman, D;Müllberg, J;Chalupny, NJ
通讯作者：
Chalupny, NJ