Th17 cells and interleukin-17 increase with poor prognosis in patients with acute myeloid leukemia.
Th17 cells and interleukin-17 increase with poor prognosis in patients with acute myeloid leukemia.
复制标题
急性髓系白血病患者Th17细胞和白细胞介素17升高且预后不良
DOI：
10.1111/cas.12459
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发表时间：
2014-08
期刊：
影响因子：
5.7
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Han Y;Ye A;Bi L;Wu J;Yu K;Zhang S
尽管Th17细胞在许多自身免疫性和炎症性疾病的发病机制中发挥了关键作用，但它们在恶性肿瘤中的作用目前仍存在争议。Th17细胞在急性髓系白血病(AML)患者中的作用和机制尚不清楚。在此，我们发现AML患者外周血和骨髓单个核细胞中Th17细胞的频率明显高于健康献血者。急性髓系白血病患者血浆IL-17、IL-22、IL-23、IL-1β、IL-6、转化生长因子-β-1水平均显著高于健康对照组。体外实验表明，IL-1β、IL-6、IL-23对人Th1 7细胞的生成和分化有促进作用，而对β-1无明显作用。IL-17A是Th17细胞分泌的标志性细胞因子，通过IL-17R诱导IL-17R阳性AML细胞的增殖，其中PI3K/Akt和Jak/STAT3信号通路的激活可能起重要作用。此外，IL-17A和IL-22联合应用可显著减少健康献血者或急性髓细胞白血病患者外周血单个核细胞Th1细胞的生成和干扰素γ的产生。Th17细胞频率高的患者预后较差，而Th1细胞频率高的患者生存期较长。Th1和Th17细胞频率的联合分析提高了预测患者预后的能力。综上所述，Th17细胞在AML的发病机制中起着至关重要的作用，可能是AML重要的治疗靶点和预后预测指标。
Although Th17 cells play crucial roles in the pathogenesis of many autoimmune and inflammatory disorders, their roles in malignancies are currently under debate. The role and mechanism of Th17 cells in patients with acute myeloid leukemia (AML) remain poorly understood. Here we demonstrated that the frequency of Th17 cells was significantly increased in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells from AML patients compared with healthy donors. Plasma levels of interleukin (IL)‐17, IL‐22, IL‐23, IL‐1β, IL‐6, and transforming growth factor (TGF)‐β1 were significantly increased in blood and bone marrow in AML patients compared with healthy donors. The in vitro experiments demonstrated that IL‐1β, IL‐6, IL‐23, but not TGF‐β1 promoted the generation and differentiation of Th17 cells from naive CD4+ T cells in humans. IL‐17A, a signature cytokine secreted by Th17 cells, induced the proliferation of IL‐17 receptor (IL‐17R)‐positive AML cells via IL‐17R, in which activation of PI3K/Akt and Jak/Stat3 signaling pathway may play important roles. In addition, combination of IL‐17A and IL‐22 significantly reduced the generation of Th1 cells and the production of interferon (IFN)‐γ from healthy donor or AML patient peripheral blood mononuclear cells. Patients with high Th17 cell frequency had poor prognosis, whereas patients with high Th1 cell frequency had prolonged survival. Combined analysis of Th1 and Th17 cell frequencies improved the ability to predict patient outcomes. In conclusion, Th17 cells play a crucial role in the pathogenesis of AML and may be an important therapeutic target and prognostic predictor.
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影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1007/s12032-013-0732-3
发表时间：
2013-12
期刊：
Medical oncology (Northwood, London, England)
影响因子：
--
作者：
Abousamra NK;Salah El-Din M;Helal R
通讯作者：
Helal R
影响因子：
30.5
作者：
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
15.9
作者：
Huber, Magdalena;Heink, Sylvia;Lohoff, Michael
通讯作者：
Lohoff, Michael