Title |
Interleukin-15 is required for immunosurveillance and immunoprevention of HER2/neu-driven mammary carcinogenesis
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Published in |
Breast Cancer Research, May 2015
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DOI | 10.1186/s13058-015-0588-x |
Pubmed ID | |
Authors |
Stefania Croci, Patrizia Nanni, Arianna Palladini, Giordano Nicoletti, Valentina Grosso, Giorgia Benegiamo, Lorena Landuzzi, Alessia Lamolinara, Marianna L. Ianzano, Dario Ranieri, Massimiliano Dall’Ora, Manuela Iezzi, Carla De Giovanni, Pier-Luigi Lollini |
Abstract |
We previously demonstrated that HER2/neu-driven mammary carcinogenesis can be prevented by an interleukin-12 (IL-12)-adjuvanted allogeneic HER2/neu-expressing cell vaccine. Since IL-12 can induce the release of interleukin-15 (IL-15), in the present study we investigated the role played by IL-15 in HER2/neu driven mammary carcinogenesis and in its immune prevention. HER2/neu transgenic mice with homozygous knockout of IL-15 (here referred to as IL15KO/NeuT mice) were compared to IL-15 wild-type HER2/neu transgenic mice (NeuT) regarding mammary carcinogenesis, profile of peripheral blood lymphocytes and splenocytes and humoral and cellular responses induced by the vaccine. IL15KO/NeuT mice showed a significantly earlier mammary cancer onset than NeuT mice, with median latency times of 16 and 20 weeks respectively, suggesting a role for IL-15 in cancer immunosurveillance. Natural killer (NK) and CD8+ lymphocytes were significantly lower in IL15KO/NeuT mice compared to mice with wild-type IL-15. The IL-12-adjuvanted allogeneic HER2/neu-expressing cell vaccine was still able to delay mammary cancer onset but efficacy in IL-15-lacking mice vanished earlier: all vaccinated IL15KO/NeuT mice developed tumors within 80 weeks of age (median latency of 53 weeks), whereas more than 70 % vaccinated NeuT mice remained tumor-free up to 80 weeks of age. Vaccinated IL15KO/NeuT mice showed less necrotic tumors with fewer CD3+ and lacked perforin-positive infiltrating cells compared to NeuT mice. Concerning the anti-vaccine antibody response, antibody titer was unaffected by the lack of IL-15, but less antibodies of IgM and IgG1 isotypes were found in IL15KO/NeuT mice. A lower induction by vaccine of systemic interferon-gamma (IFN-γ) and interleukin-5 (IL-5) was also observed in IL15KO/NeuT mice when compared to NeuT mice. Finally, we found a lower level of CD8+ memory cells in peripheral blood of vaccinated IL15KO/NeuT respect to NeuT mice. We demonstrated that IL-15 has a role in mammary cancer immunosurveillance and that IL-15-regulated NK and CD8+ memory cells play a role in long-lasting immunoprevention, further supporting the potential use of IL-15 as adjuvant in immunological strategies against tumors. |
X Demographics
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Unknown | 3 | 100% |
Demographic breakdown
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Members of the public | 2 | 67% |
Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
Geographical breakdown
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France | 1 | 2% |
Canada | 1 | 2% |
Unknown | 39 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 8 | 20% |
Researcher | 7 | 17% |
Student > Ph. D. Student | 5 | 12% |
Student > Doctoral Student | 3 | 7% |
Student > Postgraduate | 3 | 7% |
Other | 8 | 20% |
Unknown | 7 | 17% |
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Medicine and Dentistry | 10 | 24% |
Biochemistry, Genetics and Molecular Biology | 5 | 12% |
Immunology and Microbiology | 4 | 10% |
Agricultural and Biological Sciences | 4 | 10% |
Philosophy | 1 | 2% |
Other | 7 | 17% |
Unknown | 10 | 24% |