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

ABSTRACT 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. Access through your institution Buy or subscribe This is a preview of subscription content, access

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INDUCED IMMUNE CELLS ACTIVATION AND INFILTRATION IN BREAST TUMOR Article Open access 13 May 2021 IMMUNE MODULATION RESULTING FROM MR-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND IN A MODEL OF

MURINE BREAST CANCER Article Open access 13 January 2021 COMPARATIVE ANALYSIS OF THE IMMUNE RESPONSE TO RFA AND CRYOABLATION IN A COLON CANCER MOUSE MODEL Article Open access 29 October 2022

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PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS 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), and a project funded by the Priority Academic Program Development

of Jiangsu Higher Education Institutions (PAPD). AUTHOR INFORMATION Author notes * These authors contributed equally: Muxin Yu, Hong Pan, Nan Che, Li Li AUTHORS AND AFFILIATIONS * Department

of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China Muxin Yu, Hong Pan, Li Li, Yue Wang, Ge Ma, Mengjia Qian, Jiawei

Liu, Mingjie Zheng, Hui Xie, Lijun Ling, Yi Zhao, Qiang Ding, Wenbin Zhou & Shui Wang * 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 Muxin Yu, Hong Pan, Li Li, Yue Wang, Ge Ma, Mengjia Qian, Jiawei Liu, 

Qiang Ding, Wenbin Zhou & Shui Wang * Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

Nan Che * Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China Li Li * Department of Pathology, The First Affiliated Hospital of Nanjing Medical

University, 300 Guangzhou Road, Nanjing, 210029, China Cong Wang * Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029,

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W.Z. and S.W. contributed to the conception and design of the study, the analysis and interpretation of data and the revision of the article, and provided final approval of the version to

be submitted. M.Y., H.P., L.L., C.W., Y.W., G.M., M.Q., and J.L. performed the experimental study and statistical analysis and drafted and revised the article. N.C., M.Z., H.X., L.L., X.G.,

and Y.Z. participated in the clinical study, performed the statistical analysis, and drafted and revised the article. All authors read and approved the final version of the manuscript. M.Y.,

H.P., and L.L. contributed equally to this work. We would like to thank all the members of the SW and NC laboratories for helpful discussions and comments. CORRESPONDING AUTHORS

Correspondence to Wenbin Zhou or Shui Wang. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIGURE 1 SUPPLEMENTARY

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CHARACTERISTICS OF ENROLLED PATIENTS FOR MICROWAVE ABLATION AND SURGERY RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Yu, M., Pan, H., Che, N. _et al._

Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells. _Cell Mol Immunol_ 18, 2153–2164 (2021).

https://doi.org/10.1038/s41423-020-0449-0 Download citation * Received: 04 March 2020 * Accepted: 14 April 2020 * Published: 08 May 2020 * Issue Date: September 2021 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * breast cancer * microwave ablation * metastasis * NK

cells * surgery