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

被引：48

作者：

Yu, Muxin ^{[1
,2
]}

Pan, Hong ^{[1
,2
]}

Che, Nan ^{[3
]}

Li, Li ^{[1
,2
,4
]}

Wang, Cong ^{[5
]}

Wang, Yue ^{[1
,2
]}

Ma, Ge ^{[1
,2
]}

Qian, Mengjia ^{[1
,2
]}

Liu, Jiawei ^{[1
,2
]}

Zheng, Mingjie ^{[1
]}

Xie, Hui ^{[1
]}

Ling, Lijun ^{[1
]}

Zhao, Yi ^{[1
]}

Guan, Xiaoxiang ^{[6
]}

Ding, Qiang ^{[1
,2
]}

Zhou, Wenbin ^{[1
,2
]}

Wang, Shui ^{[1
,2
]}

机构：

[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Breast Surg, 300 Guangzhou Rd, Nanjing 210029, Peoples R China

[2] Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Jiangsu Collaborat Innovat Ctr Canc Personalized, Sch Publ Hlth, Nanjing 211166, Peoples R China

[3] Nanjing Med Univ, Affiliated Hosp 1, Dept Rheumatol & Immunol, 300 Guangzhou Rd, Nanjing 210029, Peoples R China

[4] Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai 200040, Peoples R China

[5] Nanjing Med Univ, Affiliated Hosp 1, Dept Pathol, 300 Guangzhou Rd, Nanjing 210029, Peoples R China

[6] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, 300 Guangzhou Rd, Nanjing 210029, Peoples R China

来源：

CELLULAR & MOLECULAR IMMUNOLOGY | 2021年 / 18卷 / 09期

基金：

中国国家自然科学基金;

关键词：

breast cancer; microwave ablation; metastasis; NK cells; surgery; RADIO-FREQUENCY ABLATION; RADIOFREQUENCY ABLATION; PRIMARY TUMOR; SPONTANEOUS REGRESSION; THERMAL ABLATION; SURGICAL REMOVAL; CARCINOMA; SURGERY; GROWTH; CRYOABLATION;

D O I：

10.1038/s41423-020-0449-0

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

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.

引用

页码：2153 / 2164

页数：12