Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer
Purpose: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. Methods: DCs were generated from mouse bone marrow or peripheral blood from healthy...
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| Tipo de documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2017 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Lenguaje: | Inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/43017 |
| Acceso en línea: | http://hdl.handle.net/11336/43017 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Breast Cancer Cpg Dendritic Cell Vaccines R848 Toll-Like Receptors https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| _version_ | 1878402763084267520 |
|---|---|
| author | Moreno Ayala, Mariela Alejandra |
| author2 | Gottardo, María Florencia Gori, María Soledad Nicola Candia, Alejandro Javier Caruso, Carla Mariana de Laurentiis, Andrea Imsen, Mercedes Klein, Slobodanka Mariana Bal, Elisa Dora Salamone, Gabriela Veronica Castro, Maria G. Seilicovich, Adriana Candolfi, Marianela |
| author2_role | author author author author author author author author author author author author |
| author_browse | Bal, Elisa Dora Candolfi, Marianela Caruso, Carla Mariana Castro, Maria G. Gori, María Soledad Gottardo, María Florencia Imsen, Mercedes Klein, Slobodanka Mariana Moreno Ayala, Mariela Alejandra Nicola Candia, Alejandro Javier Salamone, Gabriela Veronica Seilicovich, Adriana de Laurentiis, Andrea |
| author_facet | Moreno Ayala, Mariela Alejandra Gottardo, María Florencia Gori, María Soledad Nicola Candia, Alejandro Javier Caruso, Carla Mariana de Laurentiis, Andrea Imsen, Mercedes Klein, Slobodanka Mariana Bal, Elisa Dora Salamone, Gabriela Veronica Castro, Maria G. Seilicovich, Adriana Candolfi, Marianela |
| author_role | author |
| collection | CONICET Digital (CONICET) |
| description | Purpose: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. Methods: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas. Results: CpG-DCs improved the survival of tumor-bearing mice, reduced the development of lung metastases and generated immunological memory. However, dual activation of TLRs impaired the efficacy of DC vaccines. In vitro, we found that R848 inhibited CpG-mediated maturation of murine DCs. A positive feedback loop in TLR9 mRNA expression was observed upon CpG stimulation that was inhibited in the presence of R848. Impaired activation of NF-κB was detected when TLR9 and TLR7 were simultaneously activated. Blockade of nitric oxide synthase (NOS) and indoleamine-pyrrole-2,3-dioxygenase (IDO) improved the activation of CpG-DCs. When we evaluated the effect of combined activation of TLR9 and TLR7 in human DCs, we found that R848 induced robust DC activation that was inhibited by TLR9 agonists. Conclusions: These observations provide insight in the biology of TLR9 and TLR7 crosstalk and suggest caution in the selection of agonists for multiple TLR stimulation. Blockade of NOS and IDO could improve the maturation of antitumor DC vaccines. R848 could prove a useful adjuvant for DC vaccines in human patients. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | AR_003f09da60aac0b52c6d8d4e5a7b1bb4 |
| identifier_str_mv | Moreno Ayala, Mariela Alejandra; Gottardo, María Florencia; Gori, María Soledad; Nicola Candia, Alejandro Javier; Caruso, Carla Mariana; et al.; Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer; Springer; Journal Of Cancer Research And Clinical Oncology; 143; 9; 4-2017; 1713–1732 0171-5216 1432-1335 CONICET Digital CONICET |
| institution | Consejo Nacional de Investigaciones Científicas y Técnicas |
| instname_str | Consejo Nacional de Investigaciones Científicas y Técnicas |
| language | eng |
| network_acronym_str | AR |
| network_name_str | Argentina |
| oai_identifier_str | oai:ri.conicet.gov.ar:11336/43017 |
| publishDate | 2017 |
| publishDateSort | 2017 |
| publisher | Springer |
| publisherStr | Springer |
| reponame_str | CONICET Digital (CONICET) |
| spelling | Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer Moreno Ayala, Mariela Alejandra Gottardo, María Florencia Gori, María Soledad Nicola Candia, Alejandro Javier Caruso, Carla Mariana de Laurentiis, Andrea Imsen, Mercedes Klein, Slobodanka Mariana Bal, Elisa Dora Salamone, Gabriela Veronica Castro, Maria G. Seilicovich, Adriana Candolfi, Marianela Breast Cancer Cpg Dendritic Cell Vaccines R848 Toll-Like Receptors https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 Purpose: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. Methods: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas. Results: CpG-DCs improved the survival of tumor-bearing mice, reduced the development of lung metastases and generated immunological memory. However, dual activation of TLRs impaired the efficacy of DC vaccines. In vitro, we found that R848 inhibited CpG-mediated maturation of murine DCs. A positive feedback loop in TLR9 mRNA expression was observed upon CpG stimulation that was inhibited in the presence of R848. Impaired activation of NF-κB was detected when TLR9 and TLR7 were simultaneously activated. Blockade of nitric oxide synthase (NOS) and indoleamine-pyrrole-2,3-dioxygenase (IDO) improved the activation of CpG-DCs. When we evaluated the effect of combined activation of TLR9 and TLR7 in human DCs, we found that R848 induced robust DC activation that was inhibited by TLR9 agonists. Conclusions: These observations provide insight in the biology of TLR9 and TLR7 crosstalk and suggest caution in the selection of agonists for multiple TLR stimulation. Blockade of NOS and IDO could improve the maturation of antitumor DC vaccines. R848 could prove a useful adjuvant for DC vaccines in human patients. Fil: Moreno Ayala, Mariela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Gottardo, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología; Argentina Fil: Gori, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Nicola Candia, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Caruso, Carla Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología; Argentina Fil: de Laurentiis, Andrea. 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 Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina Fil: Imsen, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Klein, Slobodanka Mariana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina Fil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Salamone, Gabriela Veronica. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Castro, Maria G.. University of Michigan; Estados Unidos Fil: Seilicovich, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología; Argentina Fil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Springer http://hdl.handle.net/11336/43017 Moreno Ayala, Mariela Alejandra; Gottardo, María Florencia; Gori, María Soledad; Nicola Candia, Alejandro Javier; Caruso, Carla Mariana; et al.; Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer; Springer; Journal Of Cancer Research And Clinical Oncology; 143; 9; 4-2017; 1713–1732 0171-5216 1432-1335 CONICET Digital CONICET |
| spellingShingle | Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer Moreno Ayala, Mariela Alejandra Breast Cancer Cpg Dendritic Cell Vaccines R848 Toll-Like Receptors https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| status_str | publishedVersion |
| title | Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer |
| title_full | Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer |
| title_fullStr | Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer |
| title_full_unstemmed | Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer |
| title_short | Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer |
| title_sort | Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer |
| topic | Breast Cancer Cpg Dendritic Cell Vaccines R848 Toll-Like Receptors https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| topic_facet | Breast Cancer Cpg Dendritic Cell Vaccines R848 Toll-Like Receptors https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| url | http://hdl.handle.net/11336/43017 |