Cellular cytotoxicity is a form of immunogenic cell death
Background The immune response to cancer is often conceptualized with the cancer immunity cycle. An essential step in this interpretation is that antigens released by dying tumors are presented by dendritic cells to naive or memory T cells in the tumor-draining lymph nodes. Whether tumor cell death...
| Autores: | , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/65606 |
| Acceso en línea: | https://hdl.handle.net/10171/65606 |
| Access Level: | acceso abierto |
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Cellular cytotoxicity is a form of immunogenic cell deathMinute, L. (Luna)|||/items/7f5fd489-9a54-44f1-a8d0-167c80629de0Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30Sanchez-Paulete, A.R. (Alfonso R.)|||/items/b301b8f2-0399-464a-a885-b9b56047cfd7Ochoa-Nieto, M.C. (María del Carmen)|||/items/a26293bb-e79a-42a3-be52-dbf5208f3f89Álvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205Otano, I. (Itziar)|||/items/d3cfe573-3aef-4c87-aa71-d45016c59b03Etxeberria, I. (Iñaki)|||/items/73830f45-c05b-49ed-a21a-f7cbacfc8f07Bolaños-Mateo, E. (Elixabet)|||/items/073a1977-5579-4bd1-8604-98b3ccfd4361Azpilikueta, A. (Arantza)|||/items/8cb8f9c3-bb52-41cc-a19d-03de632308e9Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713Casares-Lagar, N. (Noelia)|||/items/32524a9b-f393-47ee-bf77-0737c65e0b7bPerez-Gracia, J.L. (Jose Luis)|||/items/7be82c5d-4858-4e04-bd77-7ef5a883021bRodriguez-Ruiz, M.E. (María Esperanza)|||/items/bb89f8c4-6380-4de3-8dd0-877dbf28ef44Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4eBackground The immune response to cancer is often conceptualized with the cancer immunity cycle. An essential step in this interpretation is that antigens released by dying tumors are presented by dendritic cells to naive or memory T cells in the tumor-draining lymph nodes. Whether tumor cell death resulting from cytotoxicity, as mediated by T cells or natural killer (NK) lymphocytes, is actually immunogenic currently remains unknown. Methods In this study, tumor cells were killed by antigenspecific T-cell receptor (TCR) transgenic CD8 T cells or activated NK cells. Immunogenic cell death was studied analyzing the membrane exposure of calreticulin and the release of high mobility group box 1 (HMGB1) by the dying tumor cells. Furthermore, the potential immunogenicity of the tumor cell debris was evaluated in immunocompetent mice challenged with an unrelated tumor sharing only one tumorassociated antigen and by class I major histocompatibility complex (MHC)-multimer stainings. Mice deficient in Batf3, Ifnar1 and Sting1 were used to study mechanistic requirements. Results We observe in cocultures of tumor cells and effector cytotoxic cells, the presence of markers of immunogenic cell death such as calreticulin exposure and soluble HMGB1 protein. Ovalbumin (OVA)-transfected MC38 colon cancer cells, exogenously pulsed to present the gp100 epitope are killed in culture by mouse gp100-specific TCR transgenic CD8 T cells. Immunization of mice with the resulting destroyed cells induces epitope spreading as observed by detection of OVA-specific T cells by MHC multimer staining and rejection of OVA+ EG7 lymphoma cells. Similar results were observed in mice immunized with cell debris generated by NK-cell mediated cytotoxicity. Mice deficient in Batf3- dependent dendritic cells (conventional dendritic cells type 1, cDC1) fail to develop an anti-OVA response when immunized with tumor cells killed by cytotoxic lymphocytes. In line with this, cultured cDC1 dendritic cells uptake and can readily cross-present antigen from cytotoxicity-killed tumor cells to cognate CD8+ T lymphocytes. Conclusion These results support that an ongoing cytotoxic antitumor immune response can lead to immunogenic tumor cell death.Dadun. Depósito Académico Digital Universidad de Navarra20232023-03-0220202020-01-0120202020-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/65606reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/656062026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Cellular cytotoxicity is a form of immunogenic cell death |
| title |
Cellular cytotoxicity is a form of immunogenic cell death |
| spellingShingle |
Cellular cytotoxicity is a form of immunogenic cell death Minute, L. (Luna)|||/items/7f5fd489-9a54-44f1-a8d0-167c80629de0 |
| title_short |
Cellular cytotoxicity is a form of immunogenic cell death |
| title_full |
Cellular cytotoxicity is a form of immunogenic cell death |
| title_fullStr |
Cellular cytotoxicity is a form of immunogenic cell death |
| title_full_unstemmed |
Cellular cytotoxicity is a form of immunogenic cell death |
| title_sort |
Cellular cytotoxicity is a form of immunogenic cell death |
| dc.creator.none.fl_str_mv |
Minute, L. (Luna)|||/items/7f5fd489-9a54-44f1-a8d0-167c80629de0 Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30 Sanchez-Paulete, A.R. (Alfonso R.)|||/items/b301b8f2-0399-464a-a885-b9b56047cfd7 Ochoa-Nieto, M.C. (María del Carmen)|||/items/a26293bb-e79a-42a3-be52-dbf5208f3f89 Álvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205 Otano, I. (Itziar)|||/items/d3cfe573-3aef-4c87-aa71-d45016c59b03 Etxeberria, I. (Iñaki)|||/items/73830f45-c05b-49ed-a21a-f7cbacfc8f07 Bolaños-Mateo, E. (Elixabet)|||/items/073a1977-5579-4bd1-8604-98b3ccfd4361 Azpilikueta, A. (Arantza)|||/items/8cb8f9c3-bb52-41cc-a19d-03de632308e9 Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713 Casares-Lagar, N. (Noelia)|||/items/32524a9b-f393-47ee-bf77-0737c65e0b7b Perez-Gracia, J.L. (Jose Luis)|||/items/7be82c5d-4858-4e04-bd77-7ef5a883021b Rodriguez-Ruiz, M.E. (María Esperanza)|||/items/bb89f8c4-6380-4de3-8dd0-877dbf28ef44 Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91 Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e |
| author |
Minute, L. (Luna)|||/items/7f5fd489-9a54-44f1-a8d0-167c80629de0 |
| author_facet |
Minute, L. (Luna)|||/items/7f5fd489-9a54-44f1-a8d0-167c80629de0 Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30 Sanchez-Paulete, A.R. (Alfonso R.)|||/items/b301b8f2-0399-464a-a885-b9b56047cfd7 Ochoa-Nieto, M.C. (María del Carmen)|||/items/a26293bb-e79a-42a3-be52-dbf5208f3f89 Álvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205 Otano, I. (Itziar)|||/items/d3cfe573-3aef-4c87-aa71-d45016c59b03 Etxeberria, I. (Iñaki)|||/items/73830f45-c05b-49ed-a21a-f7cbacfc8f07 Bolaños-Mateo, E. (Elixabet)|||/items/073a1977-5579-4bd1-8604-98b3ccfd4361 Azpilikueta, A. (Arantza)|||/items/8cb8f9c3-bb52-41cc-a19d-03de632308e9 Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713 Casares-Lagar, N. (Noelia)|||/items/32524a9b-f393-47ee-bf77-0737c65e0b7b Perez-Gracia, J.L. (Jose Luis)|||/items/7be82c5d-4858-4e04-bd77-7ef5a883021b Rodriguez-Ruiz, M.E. (María Esperanza)|||/items/bb89f8c4-6380-4de3-8dd0-877dbf28ef44 Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91 Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e |
| author_role |
author |
| author2 |
Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30 Sanchez-Paulete, A.R. (Alfonso R.)|||/items/b301b8f2-0399-464a-a885-b9b56047cfd7 Ochoa-Nieto, M.C. (María del Carmen)|||/items/a26293bb-e79a-42a3-be52-dbf5208f3f89 Álvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205 Otano, I. (Itziar)|||/items/d3cfe573-3aef-4c87-aa71-d45016c59b03 Etxeberria, I. (Iñaki)|||/items/73830f45-c05b-49ed-a21a-f7cbacfc8f07 Bolaños-Mateo, E. (Elixabet)|||/items/073a1977-5579-4bd1-8604-98b3ccfd4361 Azpilikueta, A. (Arantza)|||/items/8cb8f9c3-bb52-41cc-a19d-03de632308e9 Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713 Casares-Lagar, N. (Noelia)|||/items/32524a9b-f393-47ee-bf77-0737c65e0b7b Perez-Gracia, J.L. (Jose Luis)|||/items/7be82c5d-4858-4e04-bd77-7ef5a883021b Rodriguez-Ruiz, M.E. (María Esperanza)|||/items/bb89f8c4-6380-4de3-8dd0-877dbf28ef44 Berraondo-López, P. (Pedro)|||/items/b1f8ccc3-8e08-4ece-967c-64ccfc0e5b91 Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| description |
Background The immune response to cancer is often conceptualized with the cancer immunity cycle. An essential step in this interpretation is that antigens released by dying tumors are presented by dendritic cells to naive or memory T cells in the tumor-draining lymph nodes. Whether tumor cell death resulting from cytotoxicity, as mediated by T cells or natural killer (NK) lymphocytes, is actually immunogenic currently remains unknown. Methods In this study, tumor cells were killed by antigenspecific T-cell receptor (TCR) transgenic CD8 T cells or activated NK cells. Immunogenic cell death was studied analyzing the membrane exposure of calreticulin and the release of high mobility group box 1 (HMGB1) by the dying tumor cells. Furthermore, the potential immunogenicity of the tumor cell debris was evaluated in immunocompetent mice challenged with an unrelated tumor sharing only one tumorassociated antigen and by class I major histocompatibility complex (MHC)-multimer stainings. Mice deficient in Batf3, Ifnar1 and Sting1 were used to study mechanistic requirements. Results We observe in cocultures of tumor cells and effector cytotoxic cells, the presence of markers of immunogenic cell death such as calreticulin exposure and soluble HMGB1 protein. Ovalbumin (OVA)-transfected MC38 colon cancer cells, exogenously pulsed to present the gp100 epitope are killed in culture by mouse gp100-specific TCR transgenic CD8 T cells. Immunization of mice with the resulting destroyed cells induces epitope spreading as observed by detection of OVA-specific T cells by MHC multimer staining and rejection of OVA+ EG7 lymphoma cells. Similar results were observed in mice immunized with cell debris generated by NK-cell mediated cytotoxicity. Mice deficient in Batf3- dependent dendritic cells (conventional dendritic cells type 1, cDC1) fail to develop an anti-OVA response when immunized with tumor cells killed by cytotoxic lymphocytes. In line with this, cultured cDC1 dendritic cells uptake and can readily cross-present antigen from cytotoxicity-killed tumor cells to cognate CD8+ T lymphocytes. Conclusion These results support that an ongoing cytotoxic antitumor immune response can lead to immunogenic tumor cell death. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01 2020 2020-01-01 2023 2023-03-02 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/65606 |
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https://hdl.handle.net/10171/65606 |
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Inglés eng |
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Inglés |
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eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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