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Radiofrequency thermal ablation of breast tumors combined with intralesional administration of IL-7 and IL-15 augments anti-tumor immune responses and inhibits tumor development and metastasis

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Abstract

Tumor development or recurrence is always a matter of concern following radiofrequency thermal ablation (RFA) of tumors. To determine whether combining RFA with immunologically active cytokines might induce tumor-specific immune responses against mammary carcinoma and inhibit tumor development or metastasis, we evaluated intralesional injection of IL-7 and IL-15 in RFA-treated murine tumors. We used two different breast carcinoma models: neu-overexpressing mouse mammary carcinoma (MMC) in FVBN202 transgenic mouse and 4T1 tumors in Balb/c mouse. MMC tend to relapse even in the presence of neu-specific immune responses, and 4T1 is a weakly immunogenic, aggressive and highly metastatic transplantable tumor. In vivo growth of both of these tumors is also associated with increased numbers of CD11b+Gr1+ myeloid-derived suppressor cells (MDSC). We showed for the first time that unlike RFA alone, RFA combined with the administration of intralesional IL-7 and IL-15 (after RFA), induced immune responses to tumors, inhibited tumor development and lung metastasis, and reduced MDSC.

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Acknowledgements

This work was supported by the National Institute of Health R01 CA104757 Grant (M.H. Manjili) and flow cytometry shared resources facility supported in part by the NIH Grant P30CA16059. We gratefully acknowledge the support of VCU Massey Cancer Center and the Commonwealth Foundation for Cancer Research. The authors would like to thank the support of Mr. Robert Tucker from Angiodynamics Corp. for assisting the study by providing the RF generator and probes.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, VCU School of Medicine, Massey Cancer Center, 401 College Street, Box 980035, Richmond, VA, 23298, USA

    Mehran Habibi, Maciej Kmieciak, Laura Graham, Johanna K. Morales, Harry D. Bear & Masoud H. Manjili

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  1. Mehran Habibi
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  2. Maciej Kmieciak
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  3. Laura Graham
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  6. Masoud H. Manjili
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Correspondence to Masoud H. Manjili.

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Mehran Habibi and Maciej Kmieciak have equal contribution to the work.

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Habibi, M., Kmieciak, M., Graham, L. et al. Radiofrequency thermal ablation of breast tumors combined with intralesional administration of IL-7 and IL-15 augments anti-tumor immune responses and inhibits tumor development and metastasis. Breast Cancer Res Treat 114, 423–431 (2009). https://doi.org/10.1007/s10549-008-0024-3

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