7月22日,，NAT MED雜志在線報(bào)道,，在乳腺癌細(xì)胞沉默Irf7信號通路,，可通過誘導(dǎo)免疫逃逸,，促進(jìn)骨轉(zhuǎn)移,。
乳腺癌轉(zhuǎn)移是決定乳腺癌患者能否長期生存的關(guān)鍵因素。通過比較自發(fā)性骨轉(zhuǎn)移乳腺癌小鼠模型中原發(fā)腫瘤細(xì)胞和轉(zhuǎn)移灶腫瘤細(xì)胞的轉(zhuǎn)錄組,，研究者發(fā)現(xiàn)大量的骨轉(zhuǎn)移灶中受抑制基因是干擾素調(diào)節(jié)因子Irf7的調(diào)節(jié)靶點(diǎn),。
在腫瘤細(xì)胞中恢復(fù)Irf7或給予干擾素導(dǎo)致骨轉(zhuǎn)移減少和存活時(shí)間延長。在缺乏干擾素（IFN）受體或自然殺傷（NK）性CD8 + T細(xì)胞的反應(yīng)小鼠,，轉(zhuǎn)移的發(fā)生加速了,，這表明Irf7驅(qū)動(dòng)的轉(zhuǎn)移抑制依賴于傳導(dǎo)到宿主免疫細(xì)胞的干擾素信號。
本研究證實(shí)了這些研究結(jié)果的臨床意義：超過800位Irf7所調(diào)節(jié)的基因高表達(dá)的原發(fā)乳腺癌患者,，在無骨轉(zhuǎn)移的情況下長期生存,。根據(jù)這種基因標(biāo)志，可以識別哪些患者可受益于干擾素治療,。
由此,，本研究證實(shí)了乳腺癌細(xì)胞內(nèi)在的一條先天免疫途徑。如果抑制該途徑將妨礙免疫監(jiān)視,，從而促發(fā)腫瘤轉(zhuǎn)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.
