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| 1 | Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells显示文摘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. | Muxin Yu Hong Pan Nan Che Li Li Cong Wang Yue Wang Ge Ma Mengjia Qian Jiawei Liu Mingjie Zheng Hui Xie Lijun Ling Yi Zhao Xiaoxiang Guan Qiang Ding Wenbin Zhou Shui Wang | 2021 | Cellular & Molecular Immunology2021，18，9： | 5 |
| 2 | 基于纳米材料的肿瘤消融联合免疫治疗研究进展显示文摘影像学引导消融治疗已逐渐成为治疗不可切除实体肿瘤的重要方式,但消融治疗后存在肿瘤局部复发及全身转移风险。免疫治疗可通过增强机体自身免疫细胞功能间接清除肿瘤细胞,但多数实体肿瘤对免疫治疗的反应率较低。近年来,基于纳米材料的肿瘤消融技术发展迅速,为增强局部消融效果及提高系统免疫应答提供了新的可能。本文对基于纳米材料的消融联合免疫治疗肿瘤研究进展进行综述。 | 高龙 闫海丽 吴越 杜江锋 冯对平 | 2021 | 中国介入影像与治疗学2021，18，11： | 0 |
| 3 | Distinct roles but cooperative effect of TLR3/9 agonists and PD-1 blockade in converting the immunotolerant microenvironment of irreversible electroporation-ablated tumors显示文摘Irreversible electroporation(IRE)is a new cancer ablation technology,but methods to improve IRE-induced therapeutic immunity are only beginning to be investigated.We developed a mouse model bearing large primary(300 mm^(3))and medium distant(100 mm^(3))EG7 lymphomas engineered to express ovalbumin(OVA)as a nominal tumor antigen.We established experimental protocols including IRE alone and IRE combined with Toll-like receptor(TLR)3/9 agonists(poly I:C/CpG)(IRE+pIC/CpG),PD-1 blockade(IRE+PD-1 blockade),or both(IRE+Combo)to investigate therapeutic effects on primary and distant EG7 tumors and conversion-promoting effects on the immunotolerant tumor microenvironment(TME).We demonstrated that IRE alone simulated very weak OVA-specific CD8^(+)T cell responses and did not inhibit primary tumor growth.IRE+pIC/CpG synergistically stimulated more efficient OVA-specific CD8^(+)T cell responses and primary tumor growth inhibition than IRE+PD-1 blockade.IRE+pIC/CpG played a major role in the modulation of immune cell profiles but a minor role in the downregulation of PD-L1 expression in the TME and vice versa for IRE+PD-1 blockade.IRE+Combo cooperatively induced potent OVA-specific CD8^(+)T cell immunity and rescued exhausted intratumoral CD8^(+)T cells,leading to eradication of not only primary tumors but also untreated concomitant distant tumors and lung metastases.IRE+Combo efficiently modulated immune cell profiles,as evidenced by reductions in immunotolerant type-2(M2)macrophages,myeloid-derived suppressor-cells,plasmacytoid dendritic cells,and regulatory T cells and by increases in immunogenic M1 macrophages,CD169^(+)macrophages,type-1 conventional dendritic cells,and CD8^(+)T cells,leading to conversion of immunotolerance in not only primary TMEs but also untreated distant TMEs.IRE+Combo also showed effective therapeutic effects in two breast cancer models.Therefore,our results suggest that IRE+Combo is a promising strategy to improve IRE ablation therapy in cancer. | Fatma Babikr Jiangbo Wan Aizhang Xu Zhaojia Wu Shahid Ahmed Andrew Freywald Rajni Chibbar Yue Wu Michael Moser Gary Groot Wenjun Zhang Bing Zhang Jim Xiang | 2021 | Cellular & Molecular Immunology2021，18，12： | 0 |
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