Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
Exosomes are 60–150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from c...
| Autores principales: | , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
Elsevier
2019
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12123/4586 https://www.sciencedirect.com/science/article/pii/S0264410X19301872?via%3Dihub https://doi.org/10.1016/j.vaccine.2019.02.004 |
| _version_ | 1855483461340495872 |
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| author | Cocozza, Federico Menay, Florencia Tsacalian, Rodrigo Farid Elisei, Analia Sampedro, Pura Soria, Ivana Waldner, Claudia Inés Gravisaco, María José Mongini, Claudia |
| author_browse | Cocozza, Federico Elisei, Analia Gravisaco, María José Menay, Florencia Mongini, Claudia Sampedro, Pura Soria, Ivana Tsacalian, Rodrigo Farid Waldner, Claudia Inés |
| author_facet | Cocozza, Federico Menay, Florencia Tsacalian, Rodrigo Farid Elisei, Analia Sampedro, Pura Soria, Ivana Waldner, Claudia Inés Gravisaco, María José Mongini, Claudia |
| author_sort | Cocozza, Federico |
| collection | INTA Digital |
| description | Exosomes are 60–150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived
exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater
immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells is
limited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxic
drugs, hypoxia, acidosis, or radiation by increasing the release of EVs.
In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantly
increased EVs yield. These EVs express exosome marker proteins such as TSG-101, CD9, CD81, and
CD63. Furthermore, similar humoral and cellular immune responses were induced in vivo by EVs isolated
from LBC-tumor cells whether they were grown under normal culture conditions (EVs C) or in the presence
of cyclophosphamide (EVs CTX). Mice vaccinated either with EVs C or EVs CTX were similarly protected
against an intraperitoneal challenge with LBC tumor cells. CD4+ and CD8+ IFN-c secreting cells
were induced in immunized mice and a specific cytotoxic cellular immune response was elicited
in vitro. These results demonstrate that a Th1 response was induced by immunization with the EVs.
Our findings suggest that treatment of tumor cells with cyclophosphamide is a useful method to enhance
the secretion of EVs in sensitive cell lines without altering their antitumor properties and thus may be
used to produce antigens for future design of cancer vaccines. |
| format | Artículo |
| id | INTA4586 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2019 |
| publishDateRange | 2019 |
| publishDateSort | 2019 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA45862021-01-11T16:34:19Z Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma Cocozza, Federico Menay, Florencia Tsacalian, Rodrigo Farid Elisei, Analia Sampedro, Pura Soria, Ivana Waldner, Claudia Inés Gravisaco, María José Mongini, Claudia Ciclofosfamida Neoplasmas Respuesta Inmunológica Linfoma Vacuna Linfocitos-t Cyclophosphamide Neoplasms Immune Response Lymphoma Vaccines T-lymphocytes Extracellular Vesicles Exosomes Vesículas Extracelulares Exosomas Exosomes are 60–150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells is limited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxic drugs, hypoxia, acidosis, or radiation by increasing the release of EVs. In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantly increased EVs yield. These EVs express exosome marker proteins such as TSG-101, CD9, CD81, and CD63. Furthermore, similar humoral and cellular immune responses were induced in vivo by EVs isolated from LBC-tumor cells whether they were grown under normal culture conditions (EVs C) or in the presence of cyclophosphamide (EVs CTX). Mice vaccinated either with EVs C or EVs CTX were similarly protected against an intraperitoneal challenge with LBC tumor cells. CD4+ and CD8+ IFN-c secreting cells were induced in immunized mice and a specific cytotoxic cellular immune response was elicited in vitro. These results demonstrate that a Th1 response was induced by immunization with the EVs. Our findings suggest that treatment of tumor cells with cyclophosphamide is a useful method to enhance the secretion of EVs in sensitive cell lines without altering their antitumor properties and thus may be used to produce antigens for future design of cancer vaccines. Instituto de Virología Fil: Cocozza, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Menay, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Tsacalian, Rodrigo Farid. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Elisei, Analia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina Fil: Sampedro, Pura. Universidad de Morón. Facultad de Ciencias Exactas, Químicas y Naturales; Argentina Fil: Soria, Ivana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Waldner, Claudia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Mongini, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Morón. Facultad de Ciencias Exactas, Químicas y Naturales; Argentina 2019-03-13T13:08:41Z 2019-03-13T13:08:41Z 2019-03 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/4586 https://www.sciencedirect.com/science/article/pii/S0264410X19301872?via%3Dihub 0264-410X https://doi.org/10.1016/j.vaccine.2019.02.004 eng info:eu-repo/semantics/restrictedAccess application/pdf Elsevier Vaccine 37 (12) : 1565-1576. (14 March 2019) |
| spellingShingle | Ciclofosfamida Neoplasmas Respuesta Inmunológica Linfoma Vacuna Linfocitos-t Cyclophosphamide Neoplasms Immune Response Lymphoma Vaccines T-lymphocytes Extracellular Vesicles Exosomes Vesículas Extracelulares Exosomas Cocozza, Federico Menay, Florencia Tsacalian, Rodrigo Farid Elisei, Analia Sampedro, Pura Soria, Ivana Waldner, Claudia Inés Gravisaco, María José Mongini, Claudia Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma |
| title | Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma |
| title_full | Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma |
| title_fullStr | Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma |
| title_full_unstemmed | Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma |
| title_short | Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma |
| title_sort | cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine t cell lymphoma |
| topic | Ciclofosfamida Neoplasmas Respuesta Inmunológica Linfoma Vacuna Linfocitos-t Cyclophosphamide Neoplasms Immune Response Lymphoma Vaccines T-lymphocytes Extracellular Vesicles Exosomes Vesículas Extracelulares Exosomas |
| url | http://hdl.handle.net/20.500.12123/4586 https://www.sciencedirect.com/science/article/pii/S0264410X19301872?via%3Dihub https://doi.org/10.1016/j.vaccine.2019.02.004 |
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