Interleukin-15 is required for immunosurveillance and immunoprevention of HER2/neu-driven mammary carcinogenesis.

Autor: Croci S; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. stefania.croci@asmn.re.it.; Present address: Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Arcispedale Santa Maria Nuova-IRCCS, Viale Risorgimento 80, Reggio Emilia, 42123, Italy. stefania.croci@asmn.re.it., Nanni P; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. patrizia.nanni@unibo.it.; Interdepartmental Centre for Cancer Research 'Giorgio Prodi', University of Bologna, Via Massarenti 9, Bologna, 40138, Italy. patrizia.nanni@unibo.it., Palladini A; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. arianna.palladini@unibo.it., Nicoletti G; Laboratory of Experimental Oncology, Rizzoli Orthopedic Institute, Via di Barbiano 1/10, Bologna, 40136, Italy. giordano.nicoletti@ior.it., Grosso V; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. valentina.grosso@unibo.it., Benegiamo G; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. gbenegiamo@salk.edu., Landuzzi L; Laboratory of Experimental Oncology, Rizzoli Orthopedic Institute, Via di Barbiano 1/10, Bologna, 40136, Italy. lorena.landuzzi@ior.it., Lamolinara A; CESI Aging Research Center, G. D'Annunzio University, Via Colle dell'Ara, Chieti Scalo, Chieti, 66013, Italy. alessia.lamolinara@gmail.com., Ianzano ML; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. marianna.ianzano@unibo.it., Ranieri D; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. dario.ranieri@unibo.it., Dall'Ora M; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. massimiliano.dallora@unibo.it., Iezzi M; CESI Aging Research Center, G. D'Annunzio University, Via Colle dell'Ara, Chieti Scalo, Chieti, 66013, Italy. miezzi@unich.it., De Giovanni C; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. carla.degiovanni@unibo.it.; Interdepartmental Centre for Cancer Research 'Giorgio Prodi', University of Bologna, Via Massarenti 9, Bologna, 40138, Italy. carla.degiovanni@unibo.it., Lollini PL; Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, Bologna, 40126, Italy. pierluigi.lollini@unibo.it.; Interdepartmental Centre for Cancer Research 'Giorgio Prodi', University of Bologna, Via Massarenti 9, Bologna, 40138, Italy. pierluigi.lollini@unibo.it.
Jazyk: angličtina
Zdroj: Breast cancer research : BCR [Breast Cancer Res] 2015 May 22; Vol. 17, pp. 70. Date of Electronic Publication: 2015 May 22.
DOI: 10.1186/s13058-015-0588-x
Abstrakt: 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.
Databáze: MEDLINE
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