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

Cellular & Molecular Immunology volume 18, pages 2153–2164 (2021)Cite this article

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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.

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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).

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  1. These authors contributed equally: Muxin Yu, Hong Pan, Nan Che, Li Li

Authors and Affiliations

  1. 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

  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

    Muxin Yu, Hong Pan, Li Li, Yue Wang, Ge Ma, Mengjia Qian, Jiawei Liu, Qiang Ding, Wenbin Zhou & Shui Wang

  3. Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Nan Che

  4. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Li Li

  5. Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Cong Wang

  6. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Xiaoxiang Guan

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Contributions

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.

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Correspondence to Wenbin Zhou or Shui Wang.

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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

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