Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells
Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells
复制标题
DOI：
10.1038/nm976
复制
发表时间：
2004-01-01
期刊：
影响因子：
82.9
通讯作者：
Yu, H
中科院分区：
文献类型：
--
作者：
Wang, TH;Niu, GL;Yu, H
尽管肿瘤进展涉及诸如可激活炎症反应的组织侵入等过程，但免疫系统在很大程度上忽略或容忍播散性癌症。在癌症发展过程中阻断免疫反应启动的机制知之甚少。我们在这里报告，组成性激活的Stat-3，一个共同的致癌信号通路，抑制肿瘤表达的促炎介质。阻断肿瘤细胞中的Stat-3会增加促炎细胞因子和趋化因子的表达，这些细胞因子和趋化因子会激活先天免疫和树突状细胞，从而导致肿瘤特异性T细胞应答。此外，组成型Stat-3活性诱导抑制树突状细胞功能成熟的多效性因子的产生。肿瘤衍生因子通过祖细胞中的Stat-3激活来抑制树突状细胞成熟。因此，抗肿瘤免疫的抑制涉及Stat-3活化从肿瘤传播到树突细胞的级联反应。我们提出，肿瘤Stat-3活性可以通过阻断免疫系统多个组分产生和感知炎症信号来介导免疫逃避。
Although tumor progression involves processes such as tissue invasion that can activate inflammatory responses, the immune system largely ignores or tolerates disseminated cancers. The mechanisms that block initiation of immune responses during cancer development are poorly understood. We report here that constitutive activation of Stat-3, a common oncogenic signaling pathway, suppresses tumor expression of proinflammatory mediators. Blocking Stat-3 in tumor cells increases expression of proinflammatory cytokines and chemokines that activate innate immunity and dendritic cells, leading to tumor-specific T-cell responses. In addition, constitutive Stat-3 activity induces production of pleiotropic factors that inhibit dendritic cell functional maturation. Tumor-derived factors inhibit dendritic cell maturation through Stat-3 activation in progenitor cells. Thus, inhibition of antitumor immunity involves a cascade of Stat-3 activation propagating from tumor to dendritic cells. We propose that tumor Stat-3 activity can mediate immune evasion by blocking both the production and sensing of inflammatory signals by multiple components of the immune system.