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Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells

查看全文 作　　者：Muxin [1,2]Yu;Hong [1,2]Pan;Nan [3]Che;Li [1,2,4]Li;Cong [5]Wang;Yue [1,2]Wang;Ge [1,2]Ma;Mengjia [1,2]Qian;Jiawei [1,2]Liu;Mingjie [1]Zheng;Hui [1]Xie;Lijun [1]Ling;Yi [1]Zhao;Xiaoxiang [6]Guan;Qiang [1,2]Ding;Wenbin [1,2]Zhou;Shui [1,2]Wang 高影响力作者 机构地区：[1]Department of Breast Surgery,The First Affiliated Hospital of Nanjing Medical University,300 Guangzhou Road,Nanjing,210029,China;[2]Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine,School of Public Health,Nanjing Medical University,Nanjing,211166,China;[3]Department of Rheumatology and Immunology,The First Affiliated Hospital of Nanjing Medical University,300 Guangzhou Road,Nanjing,210029,China;[4]Department of General Surgery,Huashan Hospital,Fudan University,Shanghai,200040,China;[5]Department of Pathology,The First Affiliated Hospital of Nanjing Medical University,300 Guangzhou Road,Nanjing,210029,China;[6]Department of Oncology,The First Affiliated Hospital of Nanjing Medical University,300 Guangzhou Road,Nanjing,210029,China高影响力机构 出　　处：《Cellular & Molecular Immunology》索引2021年第18卷第9期,共12页高影响力期刊 基　　金：This work was supported in part by the National Natural Science Foundation of China(81771953);the Six Kinds of Outstanding Talent Foundation of Jiangsu Province(WSW-014,to W.Z.);the Natural Science Foundation of Jiangsu Province(BK20180108);a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD). 摘　　要：Surgery is essential for controlling the symptoms and complications of stage IV breast cancer.However,locoregional treatment of primary tumors often results in distant progression,including lung metastasis,the most common type of visceral metastasis.As a minimally invasive thermal therapy,microwave ablation(MWA)has been attempted in the treatment of breast cancer,but the innate immune response after MWA has not yet been reported.Using two murine models of stage IV breast cancer,we found that MWA of primary breast cancer inhibited the progression of lung metastasis and improved survival.NK cells were activated after MWA of the primary tumor and exhibited enhanced cytotoxic functions,and the cytotoxic pathways of NK cells were activated.Depletion experiments showed that NK cells but not CD4+or CD8+T cells played a pivotal role in prolonging survival.Then,we found that compared with surgery or control treatment,MWA of the primary tumor induced completely different NK-cell-related cytokine profiles.Macrophages were activated after MWA of the primary tumor and produced IL-15 that activated NK cells to inhibit the progression of metastasis.In addition,MWA of human breast cancer stimulated an autologous NK-cell response.These results demonstrate that MWA of the primary tumor in metastatic breast cancer inhibits metastatic progression via the macrophage/IL-15/NK-cell axis.MWA of the primary tumor may be a promising treatment strategy for de novo stage IV breast cancer,although further substantiation is essential for clinical testing. 关 键 词：breast cancer microwave ablation METASTASIS NK cells surgery
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