An oral salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T-cell-mediated immunity in celiac and portal lymph nodes : a preclinical study
Primary tumor excision is one of the most widely used therapies of cancer. However, the risk of metastases development still exists following tumor resection. The liver is a common site of metastatic disease for numerous cancers. Breast cancer is one of the most frequent sources of metastases to the...
| Autores principales: | , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
2017
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| Acceso en línea: | http://hdl.handle.net/20.500.12123/968 http://journal.frontiersin.org/article/10.3389/fimmu.2016.00072/full https://doi.org/10.3389/fimmu.2016.00072 |
| _version_ | 1855482817277853696 |
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| author | Vendrell, Alejandrina Mongini, Claudia Gravisaco, María José Canellada, Andrea Tesone, Agustina Inés Goin, Juan Carlos Waldner, Claudia Inés |
| author_browse | Canellada, Andrea Goin, Juan Carlos Gravisaco, María José Mongini, Claudia Tesone, Agustina Inés Vendrell, Alejandrina Waldner, Claudia Inés |
| author_facet | Vendrell, Alejandrina Mongini, Claudia Gravisaco, María José Canellada, Andrea Tesone, Agustina Inés Goin, Juan Carlos Waldner, Claudia Inés |
| author_sort | Vendrell, Alejandrina |
| collection | INTA Digital |
| description | Primary tumor excision is one of the most widely used therapies of cancer. However, the risk of metastases development still exists following tumor resection. The liver is a common site of metastatic disease for numerous cancers. Breast cancer is one of the most frequent sources of metastases to the liver. The aim of this work was to evaluate the efficacy of the orally administered Salmonella Typhi vaccine strain CVD 915 on the development of liver metastases in a mouse model of breast cancer. To this end, one group of
BALB/c mice was orogastrically immunized with CVD 915, while another received PBS as a control. After 24 h, mice were injected with LM3 mammary adenocarcinoma cells into the spleen and subjected to splenectomy. This oral Salmonella-based vaccine produced an antitumor effect, leading to a decrease in the number and volume of liver metastases.
Immunization with Salmonella induced an early cellular immune response in mice. This innate stimulation rendered a large production of IFN-γ by intrahepatic immune cells (IHIC) detected within 24 h. An antitumor adaptive immunity was found in the liver and celiac and portal lymph nodes (LDLN) 21 days after oral bacterial inoculation. The antitumor immune response inside the liver was associated with increased CD4+ and dendritic cell populations as well as with an inflammatory infiltrate located around liver metastatic nodules.
Enlarged levels of inflammatory cytokines (IFN-γ and TNF) were also detected in IHIC.
Furthermore, a tumor-specific production of IFN-γ and TNF as well as tumor-specific IFN- γ-producing CD8 T cells (CD8+IFN-γ+) were found in the celiac and portal lymph nodes of Salmonella-treated mice. This study provides first evidence for the involvement of LDLN in the development of an efficient cellular immune response against hepatic tumors, which resulted in the elimination of liver metastases after oral Salmonella-based vaccination. |
| format | Artículo |
| id | INTA968 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| record_format | dspace |
| spelling | INTA9682017-12-19T14:25:23Z An oral salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T-cell-mediated immunity in celiac and portal lymph nodes : a preclinical study Vendrell, Alejandrina Mongini, Claudia Gravisaco, María José Canellada, Andrea Tesone, Agustina Inés Goin, Juan Carlos Waldner, Claudia Inés Inmunidad Vacuna Salmonella Linfocitos-t Vaccines Immunity T-lymphocytes Primary tumor excision is one of the most widely used therapies of cancer. However, the risk of metastases development still exists following tumor resection. The liver is a common site of metastatic disease for numerous cancers. Breast cancer is one of the most frequent sources of metastases to the liver. The aim of this work was to evaluate the efficacy of the orally administered Salmonella Typhi vaccine strain CVD 915 on the development of liver metastases in a mouse model of breast cancer. To this end, one group of BALB/c mice was orogastrically immunized with CVD 915, while another received PBS as a control. After 24 h, mice were injected with LM3 mammary adenocarcinoma cells into the spleen and subjected to splenectomy. This oral Salmonella-based vaccine produced an antitumor effect, leading to a decrease in the number and volume of liver metastases. Immunization with Salmonella induced an early cellular immune response in mice. This innate stimulation rendered a large production of IFN-γ by intrahepatic immune cells (IHIC) detected within 24 h. An antitumor adaptive immunity was found in the liver and celiac and portal lymph nodes (LDLN) 21 days after oral bacterial inoculation. The antitumor immune response inside the liver was associated with increased CD4+ and dendritic cell populations as well as with an inflammatory infiltrate located around liver metastatic nodules. Enlarged levels of inflammatory cytokines (IFN-γ and TNF) were also detected in IHIC. Furthermore, a tumor-specific production of IFN-γ and TNF as well as tumor-specific IFN- γ-producing CD8 T cells (CD8+IFN-γ+) were found in the celiac and portal lymph nodes of Salmonella-treated mice. This study provides first evidence for the involvement of LDLN in the development of an efficient cellular immune response against hepatic tumors, which resulted in the elimination of liver metastases after oral Salmonella-based vaccination. Inst. de Biotecnología Fil: Vendrell, Alejandrina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Mongini, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Canellada, Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Tesone, Agustina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Goin, Juan Carlos. 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: Waldner, Claudia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina 2017-08-15T13:02:27Z 2017-08-15T13:02:27Z 2016 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion info:ar-repo/semantics/artículo http://hdl.handle.net/20.500.12123/968 http://journal.frontiersin.org/article/10.3389/fimmu.2016.00072/full 1664-3224 https://doi.org/10.3389/fimmu.2016.00072 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. (01 March 2016) |
| spellingShingle | Inmunidad Vacuna Salmonella Linfocitos-t Vaccines Immunity T-lymphocytes Vendrell, Alejandrina Mongini, Claudia Gravisaco, María José Canellada, Andrea Tesone, Agustina Inés Goin, Juan Carlos Waldner, Claudia Inés An oral salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T-cell-mediated immunity in celiac and portal lymph nodes : a preclinical study |
| title | An oral salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T-cell-mediated immunity in celiac and portal lymph nodes : a preclinical study |
| title_full | An oral salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T-cell-mediated immunity in celiac and portal lymph nodes : a preclinical study |
| title_fullStr | An oral salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T-cell-mediated immunity in celiac and portal lymph nodes : a preclinical study |
| title_full_unstemmed | An oral salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T-cell-mediated immunity in celiac and portal lymph nodes : a preclinical study |
| title_short | An oral salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T-cell-mediated immunity in celiac and portal lymph nodes : a preclinical study |
| title_sort | oral salmonella based vaccine inhibits liver metastases by promoting tumor specific t cell mediated immunity in celiac and portal lymph nodes a preclinical study |
| topic | Inmunidad Vacuna Salmonella Linfocitos-t Vaccines Immunity T-lymphocytes |
| url | http://hdl.handle.net/20.500.12123/968 http://journal.frontiersin.org/article/10.3389/fimmu.2016.00072/full https://doi.org/10.3389/fimmu.2016.00072 |
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