T cells remaining after intensive chemotherapy for acute myelogenous leukemia show a broad cytokine release profile including high levels of interferon-γ that can be further increased by a novel protein kinase C agonist PEP005
T cells remaining after intensive chemotherapy for acute myelogenous leukemia show a broad cytokine release profile including high levels of interferon-γ that can be further increased by a novel protein kinase C agonist PEP005
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DOI：
10.1007/s00262-006-0236-5
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发表时间：
2007-06-01
影响因子：
5.8
通讯作者：
Bruserud, Oystein
中科院分区：
文献类型：
--
作者：
Ersvær, Elisabeth;Hampson, Peter;Bruserud, Oystein
细胞因子在T细胞激活过程中释放，包括潜在的抗白血病干扰素γ (IFN γ)，以及造血生长因子粒细胞-巨噬细胞集落刺激因子（GM-CSF），这些因子可以增强急性髓性白血病（AML）细胞的增殖并抑制细胞凋亡。在本研究中，我们研究了化疗引起的细胞减少的AML患者循环T细胞释放IFN γ和GM-CSF。在T细胞天然细胞因子网络存在的情况下，用抗cd3 +抗cd28全血试验激活T细胞。我们检查了来自16名AML患者28个化疗周期的63个样本。活化的T细胞显示出广泛的细胞因子释放谱，但IFN γ和GM-CSF水平显示出显著的相关性，并且通常高于其他细胞因子水平。较高的IFN γ和GM-CSF反应与CD4:CD8比率低、患者年龄较大和未进行化疗相关，这表明T细胞激活方案对老年AML患者有潜在的效用。新型蛋白激酶C激动剂PEP005可进一步提高细胞因子水平，并诱导il - 2和TNF - α的显著产生，这可能有助于AML患者的抗肿瘤作用。我们得出结论，强化AML治疗后剩余的T细胞显示出广泛的细胞因子释放谱，包括高且显著相关的潜在抗白血病IFN γ和AML生长因子GM-CSF水平。AML引发的T细胞细胞因子反应的最终结果将取决于AML细胞的功能特征，特别是IFN γ和GM-CSF受体的相对表达，这在AML患者之间是不同的。
Cytokines are released during T cell activation, including the potentially anti-leukemic interferon-gamma (IFN gamma), but also the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) that enhance proliferation and inhibit apoptosis of acute myelogenous leukemia (AML) cells. In the present study we investigated the release of IFN gamma and GM-CSF by circulating T cells in AML patients with chemotherapy-induced cytopenia. T cells were activated with anti-CD3 plus anti-CD28 in a whole-blood assay in the presence of their natural cytokine network. We examined 63 samples derived from 16 AML patients during 28 chemotherapy cycles. Activated T cells showed a broad cytokine release profile, but IFN gamma and GM-CSF levels showed a significant correlation and were generally higher than the other cytokine levels. Higher IFN gamma and GM-CSF responses were associated with a low CD4:CD8 ratio, older patient age and no ongoing chemotherapy indicating potential utility of T cell activation regimes for the older AML patient. The cytokine levels could be further increased by the novel protein kinase C agonist PEP005, which also induced significant production of IL2 and TNF alpha which could contribute to anti-tumor effects in AML patients. We conclude that remaining T cells after intensive AML therapy show a broad cytokine release profile including high and significantly correlated levels of potentially anti-leukemic IFN gamma and the AML growth factor GM-CSF. The final outcome of an AML-initiated T cell cytokine response will thus depend on the functional characteristics of the AML cells, in particular the relative expression of IFN gamma and GM-CSF receptors which differs between AML patients.