Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response
Extracellular vesicles (EVs), including endosome-derived nanovesicles (exosomes), are involved in cell–cell communication. Through transfer of their molecular contents, extracellular nanovesicles can alter the function of recipient cells. Due to these characteristics, EVs have shown potential as a n...
| Main Authors: | , , , , , , , , , |
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| Format: | Artículo |
| Language: | Inglés |
| Published: |
2017
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.12123/497 http://journal.frontiersin.org/article/10.3389/fimmu.2017.00286/full https://doi.org/10.3389/fimmu.2017.00286 |
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| author | Menay, Florencia Herschlik, Leticia De Toro, Julieta Cocozza, Federico Tsacalian, Rodrigo Farid Gravisaco, María José Di Sciullo , Maria Paula Vendrell, Alejandrina Waldner, Claudia Inés Mongini, Claudia |
| author_browse | Cocozza, Federico De Toro, Julieta Di Sciullo , Maria Paula Gravisaco, María José Herschlik, Leticia Menay, Florencia Mongini, Claudia Tsacalian, Rodrigo Farid Vendrell, Alejandrina Waldner, Claudia Inés |
| author_facet | Menay, Florencia Herschlik, Leticia De Toro, Julieta Cocozza, Federico Tsacalian, Rodrigo Farid Gravisaco, María José Di Sciullo , Maria Paula Vendrell, Alejandrina Waldner, Claudia Inés Mongini, Claudia |
| author_sort | Menay, Florencia |
| collection | INTA Digital |
| description | Extracellular vesicles (EVs), including endosome-derived nanovesicles (exosomes), are involved in cell–cell communication. Through transfer of their molecular contents, extracellular nanovesicles can alter the function of recipient cells. Due to these characteristics, EVs have shown potential as a new alternative for cancer immunotherapy. Tumor exosomes isolated from malignant ascites can activate dendritic cells, thereby priming the immune system to recognize and kill cancer cells. However, a suppressive role on tumor immune response has also been reported, suggesting that the neoplastic stage of carcinogenesis and the microenvironment where tumor cells grow may influence the amount of EVs released by the cell. This neoplastic stage and microenvironment may also impact EVs’ components such as proteins and miRNA, determining their biological behavior. Most T-cell lymphomas have an aggressive clinical course and poor prognosis.
Consequently, complementary alternative therapies are needed to improve the survival rates achieved with conventional treatments. In this work, we have characterized EVs isolated from ascites of mice bearing a very aggressive murine T-cell lymphoma and have studied their immunogenic properties. Small EVs were isolated by differential centrifugation, ultrafiltration, and ultracentrifugation at 100,000 × g on a sucrose cushion.
The EVs were defined as exosomes by their morphology and size analyzed by electron microscopy, their floating density on a sucrose gradient, as well as their expression of endosome marker proteins ALIX, TSG-101; the tetraspanins CD63, CD9, and CD81. In addition, they contain tumor antigens, the marker for malignancy CD24, the heat shock protein HSP-70, and an unusual surface expression of HSP-90 was demonstrated. The administration of EVs isolated from ascites (EVs A) into naïve-syngeneic mice induced both humoral and cellular immune responses that allowed the rejection of subsequent tumor challenges. However, the immunization had no effect on a non-related mammary
adenocarcinoma, demonstrating that the immune response elicited was specific
and also it induced immune memory. In vitro analysis demonstrated that T-cells from EVs A-immunized mice secrete IFN-γ in response to tumor stimulation. Furthermore, tumor-specific CD4+ and CD8+ IFN-γ secreting cells could be efficiently expanded from mice immunized with EVs A, showing that a T helper 1 response is involved in tumor rejection. Our findings confirm exosomes as promising defined acellular tumor antigens for the development of an antitumor vaccine. |
| format | Artículo |
| id | INTA497 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| record_format | dspace |
| spelling | INTA4972017-12-26T12:07:04Z Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response Menay, Florencia Herschlik, Leticia De Toro, Julieta Cocozza, Federico Tsacalian, Rodrigo Farid Gravisaco, María José Di Sciullo , Maria Paula Vendrell, Alejandrina Waldner, Claudia Inés Mongini, Claudia Respuesta inmunológica Linfoma Ascitis Ratón Linfocitos-t Neoplasmas Immune Response Lymphoma Mice T-lymphocytes Extracellular vesicles (EVs), including endosome-derived nanovesicles (exosomes), are involved in cell–cell communication. Through transfer of their molecular contents, extracellular nanovesicles can alter the function of recipient cells. Due to these characteristics, EVs have shown potential as a new alternative for cancer immunotherapy. Tumor exosomes isolated from malignant ascites can activate dendritic cells, thereby priming the immune system to recognize and kill cancer cells. However, a suppressive role on tumor immune response has also been reported, suggesting that the neoplastic stage of carcinogenesis and the microenvironment where tumor cells grow may influence the amount of EVs released by the cell. This neoplastic stage and microenvironment may also impact EVs’ components such as proteins and miRNA, determining their biological behavior. Most T-cell lymphomas have an aggressive clinical course and poor prognosis. Consequently, complementary alternative therapies are needed to improve the survival rates achieved with conventional treatments. In this work, we have characterized EVs isolated from ascites of mice bearing a very aggressive murine T-cell lymphoma and have studied their immunogenic properties. Small EVs were isolated by differential centrifugation, ultrafiltration, and ultracentrifugation at 100,000 × g on a sucrose cushion. The EVs were defined as exosomes by their morphology and size analyzed by electron microscopy, their floating density on a sucrose gradient, as well as their expression of endosome marker proteins ALIX, TSG-101; the tetraspanins CD63, CD9, and CD81. In addition, they contain tumor antigens, the marker for malignancy CD24, the heat shock protein HSP-70, and an unusual surface expression of HSP-90 was demonstrated. The administration of EVs isolated from ascites (EVs A) into naïve-syngeneic mice induced both humoral and cellular immune responses that allowed the rejection of subsequent tumor challenges. However, the immunization had no effect on a non-related mammary adenocarcinoma, demonstrating that the immune response elicited was specific and also it induced immune memory. In vitro analysis demonstrated that T-cells from EVs A-immunized mice secrete IFN-γ in response to tumor stimulation. Furthermore, tumor-specific CD4+ and CD8+ IFN-γ secreting cells could be efficiently expanded from mice immunized with EVs A, showing that a T helper 1 response is involved in tumor rejection. Our findings confirm exosomes as promising defined acellular tumor antigens for the development of an antitumor vaccine. Inst. de Biotecnología Fil: Menay, Florencia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; Argentina Fil: Herschlik, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; Argentina Fil: Cocozza, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; Argentina Fil: Tsacalian, Rodrigo Farid. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; Argentina Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Di Sciullo, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina; Argentina Fil: Vendrell, Alejandrina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; Argentina Fil: Waldner, Claudia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; Argentina Fil: Mongini, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina; Argentina 2017-06-28T14:46:22Z 2017-06-28T14:46:22Z 2017-03-16 info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article http://hdl.handle.net/20.500.12123/497 http://journal.frontiersin.org/article/10.3389/fimmu.2017.00286/full https://doi.org/10.3389/fimmu.2017.00286 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Frontiers in immunology 8 : 1-14. (March 2017) |
| spellingShingle | Respuesta inmunológica Linfoma Ascitis Ratón Linfocitos-t Neoplasmas Immune Response Lymphoma Mice T-lymphocytes Menay, Florencia Herschlik, Leticia De Toro, Julieta Cocozza, Federico Tsacalian, Rodrigo Farid Gravisaco, María José Di Sciullo , Maria Paula Vendrell, Alejandrina Waldner, Claudia Inés Mongini, Claudia Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response |
| title | Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response |
| title_full | Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response |
| title_fullStr | Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response |
| title_full_unstemmed | Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response |
| title_short | Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response |
| title_sort | exosomes isolated from ascites of t cell lymphoma bearing mice expressing surface cd24 and hsp 90 induce a tumor specific immune response |
| topic | Respuesta inmunológica Linfoma Ascitis Ratón Linfocitos-t Neoplasmas Immune Response Lymphoma Mice T-lymphocytes |
| url | http://hdl.handle.net/20.500.12123/497 http://journal.frontiersin.org/article/10.3389/fimmu.2017.00286/full https://doi.org/10.3389/fimmu.2017.00286 |
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