7月22日，NAT MED杂志在线报道，在乳腺癌细胞沉默Irf7信号通路，可通过诱导免疫逃逸，促进骨转移。
乳腺癌转移是决定乳腺癌患者能否长期生存的关键因素。通过比较自发性骨转移乳腺癌小鼠模型中原发肿瘤细胞和转移灶肿瘤细胞的转录组，研究者发现大量的骨转移灶中受抑制基因是干扰素调节因子Irf7的调节靶点。
在肿瘤细胞中恢复Irf7或给予干扰素导致骨转移减少和存活时间延长。在缺乏干扰素（IFN）受体或自然杀伤（NK）性CD8 + T细胞的反应小鼠，转移的发生加速了，这表明Irf7驱动的转移抑制依赖于传导到宿主免疫细胞的干扰素信号。
本研究证实了这些研究结果的临床意义：超过800位Irf7所调节的基因高表达的原发乳腺癌患者，在无骨转移的情况下长期生存。根据这种基因标志，可以识别哪些患者可受益于干扰素治疗。
由此，本研究证实了乳腺癌细胞内在的一条先天免疫途径。如果抑制该途径将妨碍免疫监视，从而促发肿瘤转移。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape
Bradley N Bidwell,Clare Y Slaney,Nimali P Withana,Sam Forster,Yuan Cao,Sherene Loi,Daniel Andrews,Thomas Mikeska,Niamh E Mangan,Shamith A Samarajiwa,Nicole A de Weerd,Jodee Gould,Pedram Argani,Andreas M?ller,Mark J Smyth,Robin L Anderson,Paul J Hertzog& Belinda S Parker
Breast cancer metastasis is a key determinant of long-term patient survival. By comparing the transcriptomes of primary and metastatic tumor cells in a mouse model of spontaneous bone metastasis, we found that a substantial number of genes suppressed in bone metastases are targets of the interferon regulatory factor Irf7. Restoration of Irf7 in tumor cells or administration of interferon led to reduced bone metastases and prolonged survival time. In mice deficient in the interferon (IFN) receptor or in natural killer (NK) and CD8+ T cell responses, metastasis was accelerated, indicating that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. We confirmed the clinical relevance of these findings in over 800 patients in which high expression of Irf7-regulated genes in primary tumors was associated with prolonged bone metastasis–free survival. This gene signature may identify patients that could benefit from IFN-based therapies. Thus, we have identified an innate immune pathway intrinsic to breast cancer cells, the suppression of which restricts immunosurveillance to enable metastasis.
