Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors
- Autores
- Núñez, Nicolás; Berner, Fiamma; Friebel, Ekaterina; Unger, Susanne; Wyss, Nina; Martinez Gomez, Julia; Purde, Mette Triin; Niederer, Rebekka; Porsch, Maximilian; Lichtensteiger, Christa; Kramer, Rafaela; Erdmann, Michael; Schmitt, Christina; Heinzerling, Lucie; Abdou, Marie Therese; Karbach, Julia; Schadendorf, Dirk; Zimmer, Lisa; Ugurel, Selma; Klümper, Niklas; Hölzel, Michael; Power, Laura; Kreutmair, Stefanie; Capone, Mariaelena; Madonna, Gabriele; Cevhertas, Lacin; Heider, Anja; Amaral, Teresa; Hasan Ali, Omar; Bomze, David
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. Methods: In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. Findings: When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. Conclusions: We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. Funding: This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen.
Fil: Núñez, Nicolás. Universitat Zurich; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Berner, Fiamma. Medical Research Center; Suiza
Fil: Friebel, Ekaterina. Universitat Zurich; Suiza
Fil: Unger, Susanne. Universitat Zurich; Suiza
Fil: Wyss, Nina. Kantonsspital St. Gallen; Suiza. Medical Research Center; Suiza
Fil: Martinez Gomez, Julia. Universitat Zurich; Suiza
Fil: Purde, Mette Triin. Medical Research Center; Suiza
Fil: Niederer, Rebekka. Medical Research Center; Suiza. Kantonsspital St. Gallen; Suiza
Fil: Porsch, Maximilian. Kantonsspital St. Gallen; Suiza
Fil: Lichtensteiger, Christa. Kantonsspital St. Gallen; Suiza
Fil: Kramer, Rafaela. Universitat Erlangen-Nuremberg; Alemania
Fil: Erdmann, Michael. Universitat Erlangen-Nuremberg; Alemania
Fil: Schmitt, Christina. Ludwig Maximilians Universitat; Alemania
Fil: Heinzerling, Lucie. Ludwig Maximilians Universitat; Alemania. Universitat Erlangen-Nuremberg; Alemania
Fil: Abdou, Marie Therese. Kantonsspital St Gallen; Suiza
Fil: Karbach, Julia. Krankenhaus Nordwest; Alemania
Fil: Schadendorf, Dirk. German Cancer Research Center; Alemania
Fil: Zimmer, Lisa. German Cancer Research Center; Alemania
Fil: Ugurel, Selma. German Cancer Research Center; Alemania
Fil: Klümper, Niklas. Universitat Bonn; Alemania
Fil: Hölzel, Michael. Universitat Bonn; Alemania
Fil: Power, Laura. Universitat Zurich; Suiza
Fil: Kreutmair, Stefanie. Universitat Zurich; Suiza
Fil: Capone, Mariaelena. Istituto Nazionale Tumori; Italia
Fil: Madonna, Gabriele. Istituto Nazionale Tumori; Italia
Fil: Cevhertas, Lacin. Bursa Uludag University; Turquía. Universitat Zurich; Suiza
Fil: Heider, Anja. Universitat Zurich; Suiza
Fil: Amaral, Teresa. University Hospital Tübingen; Alemania. Eberhard Karls Universität Tübingen; Alemania
Fil: Hasan Ali, Omar. University of British Columbia; Canadá. Kantonsspital St Gallen; Suiza. Universitat Zurich; Suiza
Fil: Bomze, David. Kantonsspital St Gallen; Suiza. Tel Aviv University; Israel - Materia
-
BIOMARKERS FOR IMMUNOTHERAPY
CANCER IMMUNOTHERAPY
CHECKPOINT BLOCKADE
IMMUNE-RELATED ADVERSE EVENTS
TRANSLATION TO PATIENTS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/226739
Ver los metadatos del registro completo
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Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitorsNúñez, NicolásBerner, FiammaFriebel, EkaterinaUnger, SusanneWyss, NinaMartinez Gomez, JuliaPurde, Mette TriinNiederer, RebekkaPorsch, MaximilianLichtensteiger, ChristaKramer, RafaelaErdmann, MichaelSchmitt, ChristinaHeinzerling, LucieAbdou, Marie ThereseKarbach, JuliaSchadendorf, DirkZimmer, LisaUgurel, SelmaKlümper, NiklasHölzel, MichaelPower, LauraKreutmair, StefanieCapone, MariaelenaMadonna, GabrieleCevhertas, LacinHeider, AnjaAmaral, TeresaHasan Ali, OmarBomze, DavidBIOMARKERS FOR IMMUNOTHERAPYCANCER IMMUNOTHERAPYCHECKPOINT BLOCKADEIMMUNE-RELATED ADVERSE EVENTSTRANSLATION TO PATIENTShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. Methods: In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. Findings: When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. Conclusions: We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. Funding: This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen.Fil: Núñez, Nicolás. Universitat Zurich; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Berner, Fiamma. Medical Research Center; SuizaFil: Friebel, Ekaterina. Universitat Zurich; SuizaFil: Unger, Susanne. Universitat Zurich; SuizaFil: Wyss, Nina. Kantonsspital St. Gallen; Suiza. Medical Research Center; SuizaFil: Martinez Gomez, Julia. Universitat Zurich; SuizaFil: Purde, Mette Triin. Medical Research Center; SuizaFil: Niederer, Rebekka. Medical Research Center; Suiza. Kantonsspital St. Gallen; SuizaFil: Porsch, Maximilian. Kantonsspital St. Gallen; SuizaFil: Lichtensteiger, Christa. Kantonsspital St. Gallen; SuizaFil: Kramer, Rafaela. Universitat Erlangen-Nuremberg; AlemaniaFil: Erdmann, Michael. Universitat Erlangen-Nuremberg; AlemaniaFil: Schmitt, Christina. Ludwig Maximilians Universitat; AlemaniaFil: Heinzerling, Lucie. Ludwig Maximilians Universitat; Alemania. Universitat Erlangen-Nuremberg; AlemaniaFil: Abdou, Marie Therese. Kantonsspital St Gallen; SuizaFil: Karbach, Julia. Krankenhaus Nordwest; AlemaniaFil: Schadendorf, Dirk. German Cancer Research Center; AlemaniaFil: Zimmer, Lisa. German Cancer Research Center; AlemaniaFil: Ugurel, Selma. German Cancer Research Center; AlemaniaFil: Klümper, Niklas. Universitat Bonn; AlemaniaFil: Hölzel, Michael. Universitat Bonn; AlemaniaFil: Power, Laura. Universitat Zurich; SuizaFil: Kreutmair, Stefanie. Universitat Zurich; SuizaFil: Capone, Mariaelena. Istituto Nazionale Tumori; ItaliaFil: Madonna, Gabriele. Istituto Nazionale Tumori; ItaliaFil: Cevhertas, Lacin. Bursa Uludag University; Turquía. Universitat Zurich; SuizaFil: Heider, Anja. Universitat Zurich; SuizaFil: Amaral, Teresa. University Hospital Tübingen; Alemania. Eberhard Karls Universität Tübingen; AlemaniaFil: Hasan Ali, Omar. University of British Columbia; Canadá. Kantonsspital St Gallen; Suiza. Universitat Zurich; SuizaFil: Bomze, David. Kantonsspital St Gallen; Suiza. Tel Aviv University; IsraelCell Press2023-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/226739Núñez, Nicolás; Berner, Fiamma; Friebel, Ekaterina; Unger, Susanne; Wyss, Nina; et al.; Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors; Cell Press; Med; 4; 2; 2-2023; 113-1292666-63592666-6340CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.medj.2022.12.007info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2666634022005232info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:14:19Zoai:ri.conicet.gov.ar:11336/226739instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:14:19.424CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors |
| title |
Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors |
| spellingShingle |
Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors Núñez, Nicolás BIOMARKERS FOR IMMUNOTHERAPY CANCER IMMUNOTHERAPY CHECKPOINT BLOCKADE IMMUNE-RELATED ADVERSE EVENTS TRANSLATION TO PATIENTS |
| title_short |
Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors |
| title_full |
Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors |
| title_fullStr |
Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors |
| title_full_unstemmed |
Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors |
| title_sort |
Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors |
| dc.creator.none.fl_str_mv |
Núñez, Nicolás Berner, Fiamma Friebel, Ekaterina Unger, Susanne Wyss, Nina Martinez Gomez, Julia Purde, Mette Triin Niederer, Rebekka Porsch, Maximilian Lichtensteiger, Christa Kramer, Rafaela Erdmann, Michael Schmitt, Christina Heinzerling, Lucie Abdou, Marie Therese Karbach, Julia Schadendorf, Dirk Zimmer, Lisa Ugurel, Selma Klümper, Niklas Hölzel, Michael Power, Laura Kreutmair, Stefanie Capone, Mariaelena Madonna, Gabriele Cevhertas, Lacin Heider, Anja Amaral, Teresa Hasan Ali, Omar Bomze, David |
| author |
Núñez, Nicolás |
| author_facet |
Núñez, Nicolás Berner, Fiamma Friebel, Ekaterina Unger, Susanne Wyss, Nina Martinez Gomez, Julia Purde, Mette Triin Niederer, Rebekka Porsch, Maximilian Lichtensteiger, Christa Kramer, Rafaela Erdmann, Michael Schmitt, Christina Heinzerling, Lucie Abdou, Marie Therese Karbach, Julia Schadendorf, Dirk Zimmer, Lisa Ugurel, Selma Klümper, Niklas Hölzel, Michael Power, Laura Kreutmair, Stefanie Capone, Mariaelena Madonna, Gabriele Cevhertas, Lacin Heider, Anja Amaral, Teresa Hasan Ali, Omar Bomze, David |
| author_role |
author |
| author2 |
Berner, Fiamma Friebel, Ekaterina Unger, Susanne Wyss, Nina Martinez Gomez, Julia Purde, Mette Triin Niederer, Rebekka Porsch, Maximilian Lichtensteiger, Christa Kramer, Rafaela Erdmann, Michael Schmitt, Christina Heinzerling, Lucie Abdou, Marie Therese Karbach, Julia Schadendorf, Dirk Zimmer, Lisa Ugurel, Selma Klümper, Niklas Hölzel, Michael Power, Laura Kreutmair, Stefanie Capone, Mariaelena Madonna, Gabriele Cevhertas, Lacin Heider, Anja Amaral, Teresa Hasan Ali, Omar Bomze, David |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
BIOMARKERS FOR IMMUNOTHERAPY CANCER IMMUNOTHERAPY CHECKPOINT BLOCKADE IMMUNE-RELATED ADVERSE EVENTS TRANSLATION TO PATIENTS |
| topic |
BIOMARKERS FOR IMMUNOTHERAPY CANCER IMMUNOTHERAPY CHECKPOINT BLOCKADE IMMUNE-RELATED ADVERSE EVENTS TRANSLATION TO PATIENTS |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. Methods: In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. Findings: When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. Conclusions: We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. Funding: This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen. Fil: Núñez, Nicolás. Universitat Zurich; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Berner, Fiamma. Medical Research Center; Suiza Fil: Friebel, Ekaterina. Universitat Zurich; Suiza Fil: Unger, Susanne. Universitat Zurich; Suiza Fil: Wyss, Nina. Kantonsspital St. Gallen; Suiza. Medical Research Center; Suiza Fil: Martinez Gomez, Julia. Universitat Zurich; Suiza Fil: Purde, Mette Triin. Medical Research Center; Suiza Fil: Niederer, Rebekka. Medical Research Center; Suiza. Kantonsspital St. Gallen; Suiza Fil: Porsch, Maximilian. Kantonsspital St. Gallen; Suiza Fil: Lichtensteiger, Christa. Kantonsspital St. Gallen; Suiza Fil: Kramer, Rafaela. Universitat Erlangen-Nuremberg; Alemania Fil: Erdmann, Michael. Universitat Erlangen-Nuremberg; Alemania Fil: Schmitt, Christina. Ludwig Maximilians Universitat; Alemania Fil: Heinzerling, Lucie. Ludwig Maximilians Universitat; Alemania. Universitat Erlangen-Nuremberg; Alemania Fil: Abdou, Marie Therese. Kantonsspital St Gallen; Suiza Fil: Karbach, Julia. Krankenhaus Nordwest; Alemania Fil: Schadendorf, Dirk. German Cancer Research Center; Alemania Fil: Zimmer, Lisa. German Cancer Research Center; Alemania Fil: Ugurel, Selma. German Cancer Research Center; Alemania Fil: Klümper, Niklas. Universitat Bonn; Alemania Fil: Hölzel, Michael. Universitat Bonn; Alemania Fil: Power, Laura. Universitat Zurich; Suiza Fil: Kreutmair, Stefanie. Universitat Zurich; Suiza Fil: Capone, Mariaelena. Istituto Nazionale Tumori; Italia Fil: Madonna, Gabriele. Istituto Nazionale Tumori; Italia Fil: Cevhertas, Lacin. Bursa Uludag University; Turquía. Universitat Zurich; Suiza Fil: Heider, Anja. Universitat Zurich; Suiza Fil: Amaral, Teresa. University Hospital Tübingen; Alemania. Eberhard Karls Universität Tübingen; Alemania Fil: Hasan Ali, Omar. University of British Columbia; Canadá. Kantonsspital St Gallen; Suiza. Universitat Zurich; Suiza Fil: Bomze, David. Kantonsspital St Gallen; Suiza. Tel Aviv University; Israel |
| description |
Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. Methods: In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. Findings: When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. Conclusions: We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. Funding: This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-02 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
| format |
article |
| status_str |
publishedVersion |
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http://hdl.handle.net/11336/226739 Núñez, Nicolás; Berner, Fiamma; Friebel, Ekaterina; Unger, Susanne; Wyss, Nina; et al.; Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors; Cell Press; Med; 4; 2; 2-2023; 113-129 2666-6359 2666-6340 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/226739 |
| identifier_str_mv |
Núñez, Nicolás; Berner, Fiamma; Friebel, Ekaterina; Unger, Susanne; Wyss, Nina; et al.; Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors; Cell Press; Med; 4; 2; 2-2023; 113-129 2666-6359 2666-6340 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.medj.2022.12.007 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2666634022005232 |
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application/pdf application/pdf |
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Cell Press |
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Cell Press |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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