Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
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DOI：
10.1038/nm.3708
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发表时间：
2014-11-01
期刊：
影响因子：
82.9
通讯作者：
Zitvogel, Laurence
中科院分区：
文献类型：
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作者：
Sistigu, Antonella;Yamazaki, Takahiro;Zitvogel, Laurence
蒽环类药物在小鼠体内的一些抗肿瘤作用源于诱导先天和T细胞介导的抗癌免疫反应。在这里，我们证明了在激活内体模式识别受体Toll样受体3(TLR3)后，蒽环类药物刺激恶性肿瘤细胞快速产生I型干扰素(IFN)。通过与肿瘤细胞上的干扰素-α和干扰素-β受体(IFNAR)结合，I型IFN触发自分泌和旁分泌电路，导致趋化因子(C-X-C基序)配体10(CXCL10)的释放。缺乏TIR3或Ifnar的肿瘤对化疗无效，除非分别人工提供I型干扰素或CxCl10。此外，I型干扰素相关信号可预测预后较差的几个独立乳腺癌患者对基于蒽环类药物的化疗的临床反应。我们的数据表明，蒽环素介导的免疫反应类似于病毒病原体诱导的免疫反应。我们推测，这种“病毒模仿”构成了化疗成功的标志。
Some of the anti-neoplastic effects of anthracyclines in mice originate from the induction of innate and T cell-mediated anticancer immune responses. Here we demonstrate that anthracyclines stimulate the rapid production of type I interferons (IFNs) by malignant cells after activation of the endosomal pattern recognition receptor Toll-like receptor 3 (TLR3). By binding to IFN-alpha and IFN-beta receptors (IFNARs) on neoplastic cells, type I IFNs trigger autocrine and paracrine circuitries that result in the release of chemokine (C-X-C motif) ligand 10 (CXCL10). Tumors lacking TIr3 or Ifnar failed to respond to chemotherapy unless type I IFN or Cxcl10, respectively, was artificially supplied. Moreover, a type I IFN-related signature predicted clinical responses to anthracycline-based chemotherapy in several independent cohorts of patients with breast carcinoma characterized by poor prognosis. Our data suggest that anthracycline-mediated immune responses mimic those induced by viral pathogens. We surmise that such 'viral mimicry' constitutes a hallmark of successful chemotherapy.