The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity.
The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity.
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DOI：
10.1158/0008-5472.can-10-2820
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发表时间：
2011-04-01
期刊：
影响因子：
11.2
通讯作者：
Auh SL
中科院分区：
文献类型：
--
作者：
Burnette BC;Liang H;Lee Y;Chlewicki L;Khodarev NN;Weichselbaum RR;Fu YX;Auh SL
局部放射疗法（RT）的效率最广泛的解释是基于通过诱导致命DNA损伤对癌细胞的直接细胞毒性，这表明局部消融肿瘤可以导致T细胞启动和T细胞的增加细胞依赖性肿瘤回归，但在这里尚不清楚，我们描述了I型干扰素（IFN）的重要作用RT。我们表明，消融RT增加了IFNβ的肿瘤内产生，更令人惊讶的是，RT的抗肿瘤效应在I型IFN非反应性宿主中被取消。 RT大大增强了野生型小鼠的肿瘤渗透DC的交叉染色能力，但IFN受体不足的小鼠肿瘤的交叉渗透能力增强。 RT后的DC依赖于使用腺病毒介导的IFNβ表达的I型IFN的自分泌产生我们的研究完全回归。
The most widely held explanation for the efficacy of local radiotherapy (RT) is based on direct cytotoxicity to cancer cells through the induction of lethal DNA damage. Recent studies have demonstrated that local ablative radiation of established tumors can lead to increased T cell priming and T cell dependent tumor regression, but the underlying mechanism remains unclear. Here, we describe an essential role for type I interferon (IFN) in local tumor control mediated by local RT. We show that ablative RT increases intratumoral production of IFNβ and, more surprisingly, the anti-tumor effect of RT is abolished in type I IFN non-responsive hosts. Furthermore, the major target of RT-induced type I IFN is the hematopoietic compartment. RT drastically enhances the cross-priming capacity of tumor infiltrating DC from wild-type mice but not type I IFN receptor deficient mice. The enhanced cross-priming ability of tumor infiltrating DCs after RT was dependent on autocrine production of type I IFNs. Using adenoviral-mediated expression of IFNβ, we demonstrate that delivery of exogenous IFNβ into the tumor tissue in the absence of RT is also sufficient to selectively expand antigen-specific T cells leading to complete tumor regression. Our study reveals that local high-dose RT can trigger production of type I IFN that initiates a cascading innate and adaptive immune attack on the tumor.