Nat. Med. :乳腺癌细胞能够关闭干扰素生产和躲避免疫反应

干扰素是一种免疫反应蛋白，身体利用这种蛋白对抗病毒和细菌感染。在一项新研究中，研究人员发现某些乳腺癌细胞能够关闭负责导致干扰素产生的基因。因为这一发现，于2012年7月22日在线发表在Nature Medicine期刊上的一篇论文中，他们写道，癌细胞能够在不遭受免疫系统攻击的情况下转移到身体其他部分，特别是骨组织中。

在这项新研究中，为了更好地了解当癌症从乳腺转移到身体其他部分时会发生什么，研究人员从乳腺癌病人和小鼠解剖标本中收集组织样品。在研究这些样品过程中，他们发现癌细胞能够关闭癌症转移到身体其他部分的人和小鼠中的基因IRF7。当检测到感染存在时，IRF7负责促进干扰素产生。抑制干扰素产生而阻止免疫反应，从而使得癌细胞轻易地转移到骨髓中。因此，癌细胞能够伪装它们的存在并躲避它们的攻击者。

为了抵消这种效果，研究人员尝试了两种方法。在第一种方法中，他们试着以癌细胞不能关闭干扰素产生的方式将干扰素基因导入细胞内。第二种方法涉及将干扰素注射到实验小鼠体内。他们报道这两种方法都能有效地阻止癌细胞转移。不过，他们也说，在病人能够接受这些治疗之前，还需开展更多测试。

本文编译自Study finds breast cancer cells able to turn off interferon production to avoid immune response

doi: 10.1038/nm.2830
PMC:
PMID:

Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape

Bradley N Bidwell, Clare Y Slaney, Nimali P Withana et al.

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.