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http://purl.uniprot.org/citations/25997501http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25997501http://www.w3.org/2000/01/rdf-schema#comment"

Introduction

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 immunoprevention.

Methods

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.

Results

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 % of vaccinated NeuT mice remained tumor-free up to 80 weeks of age. Vaccinated IL15KO/NeuT mice showed less necrotic tumors with fewer CD3+ lymphocyes 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 the peripheral blood of vaccinated IL15KO/NeuT mice compared to NeuT mice.

Conclusions

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."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.org/dc/terms/identifier"doi:10.1186/s13058-015-0588-x"xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Croci S."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Nicoletti G."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Benegiamo G."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Nanni P."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Iezzi M."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Ranieri D."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Grosso V."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Palladini A."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"De Giovanni C."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Landuzzi L."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Lollini P.L."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Ianzano M.L."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Lamolinara A."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/author"Dall'Ora M."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/name"Breast Cancer Res"xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/pages"70"xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/title"Interleukin-15 is required for immunosurveillance and immunoprevention of HER2/neu-driven mammary carcinogenesis."xsd:string
http://purl.uniprot.org/citations/25997501http://purl.uniprot.org/core/volume"17"xsd:string
http://purl.uniprot.org/citations/25997501http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25997501
http://purl.uniprot.org/citations/25997501http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25997501
http://purl.uniprot.org/uniprot/#_A0A1B0GQZ2-mappedCitation-25997501http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25997501
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