Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells
Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells
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DOI：
10.1182/blood-2009-10-248245
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发表时间：
2010-11-11
期刊：
影响因子：
20.3
通讯作者：
Airoldi, Irma
中科院分区：
文献类型：
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作者：
Cocco, Claudia;Canale, Sara;Airoldi, Irma
白细胞介素 (IL)-23 是属于 IL-12 超家族的促炎细胞因子。 IL-23的抗肿瘤活性存在争议，目前尚不清楚该细胞因子是否可以直接作用于肿瘤细胞。本研究的目的是研究 IL-23 在儿童 B 急性淋巴细胞白血病 (B-ALL) 细胞中潜在的直接抗肿瘤活性，并揭示其相关分子机制。在这里，我们首次表明，与正常早期 B 淋巴细胞相比，IL-23R 在原代 B-ALL 细胞中上调，并且 IL-23 通过抑制肿瘤细胞增殖和诱导细胞凋亡，在体外和体内直接抑制肿瘤生长。后一项发现与儿科 B-ALL 细胞中 IL-23 诱导的 miR15a 表达上调以及随后的 BCL-2 蛋白表达下调有关。这项研究表明 IL-23 具有抗白血病活性并揭示了其潜在机制。因此，IL-23可能是治疗对当前治疗标准无反应的B-ALL患者的候选新药。 （血。2010；116（19）：3887-3898）
Interleukin (IL)-23 is a proinflammatory cytokine belonging to the IL-12 superfamily. The antitumor activity of IL-23 is controversial, and it is unknown whether or not the cytokine can act directly on tumor cells. The aim of this study was to investigate the potential direct antitumor activity of IL-23 in pediatric B-acute lymphoblastic leukemia (B-ALL) cells and to unravel the molecular mechanisms involved. Here, we show, for the first time, that IL-23R is up-regulated in primary B-ALL cells, compared with normal early B lymphocytes, and that IL-23 dampens directly tumor growth in vitro and in vivo through the inhibition of tumor cell proliferation and induction of apoptosis. The latter finding is related to IL-23-induced upregulation of miR15a expression and the consequent down-regulation of BCL-2 protein expression in pediatric B-ALL cells. This study demonstrates that IL-23 possesses antileukemic activity and unravels the underlying mechanisms. Thus, IL-23 may be a candidate novel drug for the treatment of B-ALL patients unresponsive to current therapeutic standards. (Blood. 2010; 116(19):3887-3898)