Deregulation of STING Signaling in Colorectal Carcinoma Constrains DNA Damage Responses and Correlates With Tumorigenesis.
Deregulation of STING Signaling in Colorectal Carcinoma Constrains DNA Damage Responses and Correlates With Tumorigenesis.
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DOI：
10.1016/j.celrep.2015.12.029
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发表时间：
2016-01-12
期刊：
影响因子：
8.8
通讯作者：
Barber GN
中科院分区：
文献类型：
--
作者：
Xia T;Konno H;Ahn J;Barber GN
STING（干扰素基因刺激因子）已被证明对于控制抗病毒反应以及抗肿瘤适应性免疫至关重要，但关于其在人类肿瘤中的调节知之甚少。在这里，我们报告说，STING信号在包括结直肠癌在内的各种癌症中被反复抑制。STING信号传导的丧失阻碍了DNA损伤应答，该DNA损伤应答负责产生促进组织修复和抗肿瘤T细胞引发的关键细胞因子，例如I型干扰素（IFN）。相应地，缺陷STING功能也高度预测有效的DNA病毒介导的溶瘤活性。因此，受损的STING反应可能使受损细胞逃避宿主免疫监视过程，尽管提供了一个关键的预后测量，可以帮助预测有效的肿瘤病毒治疗的结果。
STING (stimulator of interferon genes) has been shown to be critical for controlling anti-viral responses, as well as anti-tumor adaptive immunity but little is known regarding its regulation in human tumors. Here, we report that STING-signaling is recurrently suppressed in a wide variety of cancers, including colorectal carcinoma. Loss of STING signaling impeded DNA damage responses accountable for generating key cytokines that facilitate tissue repair and anti-tumor-T cell priming, such as type I interferon (IFN). Correspondingly, defective STING function was also highly predictive of effectual DNA virus-mediated oncolytic activity. Thus, impaired STING responses may enable damaged cells to evade host immunosurveillance processes, although provides a critical prognostic measurement that could help predict the outcome to effective oncoviral therapy.