Mesenchymal stem cells derived from low risk acute lymphoblastic leukemia patients promote NK cell antitumor activity
Mesenchymal stem cells derived from low risk acute lymphoblastic leukemia patients promote NK cell antitumor activity
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DOI：
10.1016/j.canlet.2015.04.012
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发表时间：
2015-07-28
期刊：
影响因子：
9.7
通讯作者：
Vicente, Angeles
中科院分区：
文献类型：
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作者：
Entrena, Ana;Varas, Alberto;Vicente, Angeles
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）是骨髓微环境的重要组成部分，在维持造血干细胞生态位、调节先天免疫和获得性免疫等方面发挥重要作用。我们分析了来自急性淋巴细胞白血病（ALL）患者的MSC的免疫生物学及其对NK细胞功能的影响。与来自健康供体的MSC（Healthy-MSC）对免疫应答的抑制作用相反，我们证明了来自诊断时的低/中等风险ALL患者的MSC（ALL-MSC）促进有效的NM细胞应答，包括细胞因子产生、表型活化和最重要的细胞毒性。纵向研究表明，ALL-MSC的这些免疫刺激作用逐渐减弱。当暴露于白血病细胞时，健康的MSC采用ALL-MSC样免疫调节特征，获得刺激NI（细胞抗肿瘤功能）的能力。ALL-MSC的这些功能变化的潜在机制包括可溶性抑制因子的产生减少、共刺激和共抑制分子的差异表达、特异性TLR的表达增加和Notch途径活化。总的来说，我们的研究结果表明，在对白血病细胞的反应中，ALL-MSC可以通过刺激抗肿瘤的先天免疫应答来介导宿主有益的免疫调节作用。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Mesenchymal stem cells (MSCs) are key components of the bone marrow microenvironment which contribute to the maintenance of the hematopoietic stem cell niche and exert immunoregulatory functions in innate and adaptive immunity. We analyze the immunobiology of MSCs derived from acute lymphoblastic leukemia (ALL) patients and their impact on NK cell function. In contrast to the inhibitory effects on the immune response exerted by MSCs from healthy donors (Healthy-MSCs), we demonstrate that MSCs derived from low/intermediate risk ALL patients at diagnosis (ALL-MSCs) promote an efficient NM cell response including cytokine production, phenotypic activation and most importantly, cytotoxicity. Longitudinal studies indicate that these immunostimulatory effects of ALL-MSCs are progressively attenuated. Healthy-MSCs adopt ALL-MSC-like immunomodulatory features when exposed to leukemia cells, acquiring the ability to stimulate NI( cell antitumor function. The mechanisms underlying to these functional changes of ALL-MSCs include reduced production of soluble inhibitory factors, differential expression of costimulatory and coinhibitory molecules, increased expression of specific TLRs and Notch pathway activation. Collectively our findings indicate that, in response to leukemia cells, ALL-MSCs could mediate a host beneficial immunomodulatory effect by stimulating the antitumor innate immune response. (C) 2015 Elsevier Ireland Ltd. All rights reserved.