三阴乳腺癌(TNBC)，至今无靶向药物可用。巨噬细胞(Mφ)极化异常可促进上皮间质转化(EMT)，EMT促进的迁移、侵袭是TNBC易转移、预后差的重要原因。我们已确证溶瘤甲病毒能特异性靶向破坏TNBC。对VCP(它将窖蛋白1送往溶酶体降解)的抑制，可在Mφ提高窖蛋白1表达，在溶瘤病毒治疗的TNBC小鼠促进Mφ激活和小鼠存活。窖蛋白1对Mφ如何作用？与TNBC关系如何？我们提出“窖蛋白1可通过抑制TGF-β通路促进Mφ再极化，抑制EMT，免疫协同增效病毒溶瘤”的假说。我们拟采用过表达、显性阴性突变等手段干预窖蛋白1或TGF-β后利用PCR，ELISA、流式、共聚焦等研究Mφ的再极化，共培养法研究Mφ对单核细胞趋化以及TNBC迁移、侵袭、EMT的影响。最后，将利用TNBC皮下或原位移植瘤及转移癌模型小鼠确证窖蛋白1与溶瘤甲病毒的协同抗癌作用。本研究将为溶瘤病毒的Mφ相关免疫协同研究提供新思路。

So far, there is no target drugs available for three negative breast cancer (TNBC). Macrophages (MΦ) polarization anomalies can promote the epithelial mesenchymal transition (EMT), cancer cell invasion and migration promoted by EMT are the important causes of the metastasis and poor prognosis TNBC. We previously confirmed that oncolytic virus can be safely and effectively targeted tumor TNBC for destruction. Further, during the process of attacking cancer tissue by oncolytic virus，we use VCP inhibitor (a protein capable of trafficking CAV1 to lysosomes) to downregulate the degradation of CAV1. And, we found that the downregulated degradation of CAV1 can increase the infiltration and activation of MΦ in tumor. How does CAV1 play the role on MΦ? And, what is the role of CAV1 on TNBC? We put forward the hypothesis of "Through inhibition of TGF-βpathway, CAV1 promotes repolarization of MΦ, inhibition of EMT, reduce the tumor invasion and metastasis". We intend to use RNAi methods and the overexpression of wild type or dominant negative mutants to intervene CAV1/TGF-β pathway. After intervention, using quantitative PCR, confocal microscopy and flow cytometry techniques to study the changes related to MΦ. Using co-culture system to study the effect of MΦ on the EMT, migration and invasion of TNBC under the regulation of CAV1/TGF-β. Finally, using immunocompetent TNBC model to confirm the synergy effect of CAV1 and oncolytic virus for anticancer. This study will shed a light on the research for synergistic effect combining MΦ and oncolytic virus.