Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine Melanoma
Cancer immunotherapy is currently one of the leading approaches in cancer treatment. Gene electrotransfer of plasmids encoding interleukin 12 (IL-12) into the cells leads to the production of IL-12, which drives immune cell polarization to an antitumoral response. One of the cell types that shows gr...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/5285890 |
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| author | Ursa Lampreht Tratar Luisa Loiacono Maja Cemazar Urska Kamensek Vito Michele Fazio Gregor Sersa Emanuela Signori |
| author_facet | Ursa Lampreht Tratar Luisa Loiacono Maja Cemazar Urska Kamensek Vito Michele Fazio Gregor Sersa Emanuela Signori |
| author_sort | Ursa Lampreht Tratar |
| collection | DOAJ |
| description | Cancer immunotherapy is currently one of the leading approaches in cancer treatment. Gene electrotransfer of plasmids encoding interleukin 12 (IL-12) into the cells leads to the production of IL-12, which drives immune cell polarization to an antitumoral response. One of the cell types that shows great promise in targeting tumor cells under the influence of IL-12 cytokine milieu is that of macrophages. Therefore, the aim of this study was to evaluate gene electrotransfer of antibiotic resistance-free plasmid DNA-encoding murine IL-12 (mIL-12) in mice bearing aggressive B16F10 murine melanoma. IL-12 electrotransfer resulted in the complete long-term eradication of the tumors. Serum mIL-12 and murine interferon γ (mIFNγ) were increased after IL-12 gene electrotransfer. Further on, hematoxylin and eosin (HE) staining showed increased infiltration of immune cells that lasted from day 4 until day 14. Immunohistochemistry (IHC) staining of F4/80, MHCII, and CD11c showed higher positive staining in the IL-12 gene electrotransfer group than in the control groups. Immune cell infiltration into the tumors and the high density of MHCII- and CD11c-positive cells suggest an antitumor polarization of macrophages and the presence of antigen-presenting cells that contributes to the important antitumor effectiveness of IL-12. |
| format | Article |
| id | doaj-art-adafbeca0d9c4413bfb7b72f718abbcd |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-adafbeca0d9c4413bfb7b72f718abbcd2025-08-20T02:20:34ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/52858905285890Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine MelanomaUrsa Lampreht Tratar0Luisa Loiacono1Maja Cemazar2Urska Kamensek3Vito Michele Fazio4Gregor Sersa5Emanuela Signori6Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, Ljubljana, SloveniaLaboratory of Genetic and Clinical Pathology, University Campus Bio-Medico of Rome, Via Álvaro del Portillo 21, 00128 Rome, ItalyDepartment of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, Ljubljana, SloveniaDepartment of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, Ljubljana, SloveniaLaboratory of Genetic and Clinical Pathology, University Campus Bio-Medico of Rome, Via Álvaro del Portillo 21, 00128 Rome, ItalyDepartment of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, Ljubljana, SloveniaLaboratory of Genetic and Clinical Pathology, University Campus Bio-Medico of Rome, Via Álvaro del Portillo 21, 00128 Rome, ItalyCancer immunotherapy is currently one of the leading approaches in cancer treatment. Gene electrotransfer of plasmids encoding interleukin 12 (IL-12) into the cells leads to the production of IL-12, which drives immune cell polarization to an antitumoral response. One of the cell types that shows great promise in targeting tumor cells under the influence of IL-12 cytokine milieu is that of macrophages. Therefore, the aim of this study was to evaluate gene electrotransfer of antibiotic resistance-free plasmid DNA-encoding murine IL-12 (mIL-12) in mice bearing aggressive B16F10 murine melanoma. IL-12 electrotransfer resulted in the complete long-term eradication of the tumors. Serum mIL-12 and murine interferon γ (mIFNγ) were increased after IL-12 gene electrotransfer. Further on, hematoxylin and eosin (HE) staining showed increased infiltration of immune cells that lasted from day 4 until day 14. Immunohistochemistry (IHC) staining of F4/80, MHCII, and CD11c showed higher positive staining in the IL-12 gene electrotransfer group than in the control groups. Immune cell infiltration into the tumors and the high density of MHCII- and CD11c-positive cells suggest an antitumor polarization of macrophages and the presence of antigen-presenting cells that contributes to the important antitumor effectiveness of IL-12.http://dx.doi.org/10.1155/2017/5285890 |
| spellingShingle | Ursa Lampreht Tratar Luisa Loiacono Maja Cemazar Urska Kamensek Vito Michele Fazio Gregor Sersa Emanuela Signori Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine Melanoma Mediators of Inflammation |
| title | Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine Melanoma |
| title_full | Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine Melanoma |
| title_fullStr | Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine Melanoma |
| title_full_unstemmed | Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine Melanoma |
| title_short | Gene Electrotransfer of Plasmid-Encoding IL-12 Recruits the M1 Macrophages and Antigen-Presenting Cells Inducing the Eradication of Aggressive B16F10 Murine Melanoma |
| title_sort | gene electrotransfer of plasmid encoding il 12 recruits the m1 macrophages and antigen presenting cells inducing the eradication of aggressive b16f10 murine melanoma |
| url | http://dx.doi.org/10.1155/2017/5285890 |
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