Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma

Autores
Kristensen, Nikolaj Pagh; Heeke, Christina; Tvingsholm, Siri A.; Borch, Annie; Draghi, Arianna; Crowther, Michael D.; Carri, Ibel; Munk, Kamilla K.; Holm, Jeppe Sejerø; Bjerregaard, Anne Mette; Bentzen, Amalie Kai; Marquard, Andrea M.; Szallasi, Zoltan; McGranahan, Nicholas; Andersen, Rikke; Nielsen, Morten; Jönsson, Göran B.; Donia, Marco; Svane, Inge Marie; Hadrup, Sine Reker
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND. Neoantigen-driven recognition and T cell–mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs). Yet how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells.
Fil: Kristensen, Nikolaj Pagh. Technical University of Denmark; Dinamarca
Fil: Heeke, Christina. Technical University of Denmark; Dinamarca
Fil: Tvingsholm, Siri A.. Technical University of Denmark; Dinamarca
Fil: Borch, Annie. Technical University of Denmark; Dinamarca
Fil: Draghi, Arianna. Copenhagen University Hospital; Dinamarca
Fil: Crowther, Michael D.. Copenhagen University Hospital; Dinamarca
Fil: Carri, Ibel. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Munk, Kamilla K.. Technical University of Denmark; Dinamarca
Fil: Holm, Jeppe Sejerø. Technical University of Denmark; Dinamarca
Fil: Bjerregaard, Anne Mette. Technical University of Denmark; Dinamarca
Fil: Bentzen, Amalie Kai. Technical University of Denmark; Dinamarca
Fil: Marquard, Andrea M.. Technical University of Denmark; Dinamarca
Fil: Szallasi, Zoltan. Danish Cancer Society Research Center; Dinamarca
Fil: McGranahan, Nicholas. University College London; Estados Unidos
Fil: Andersen, Rikke. Copenhagen University Hospital; Dinamarca
Fil: Nielsen, Morten. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Jönsson, Göran B.. Faculty Of Medicine ; Lund University;
Fil: Donia, Marco. Copenhagen University Hospital; Dinamarca
Fil: Svane, Inge Marie. Copenhagen University Hospital; Dinamarca
Fil: Hadrup, Sine Reker. Technical University of Denmark; Dinamarca
Materia
Cancer immunotherapy
Immunology
Melanoma
T cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/214381
Acceder
id CONICETDig_93bafbc1343c56859012cfd50089a722
oai_identifier_str oai:ri.conicet.gov.ar:11336/214381
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanomaKristensen, Nikolaj PaghHeeke, ChristinaTvingsholm, Siri A.Borch, AnnieDraghi, AriannaCrowther, Michael D.Carri, IbelMunk, Kamilla K.Holm, Jeppe SejerøBjerregaard, Anne MetteBentzen, Amalie KaiMarquard, Andrea M.Szallasi, ZoltanMcGranahan, NicholasAndersen, RikkeNielsen, MortenJönsson, Göran B.Donia, MarcoSvane, Inge MarieHadrup, Sine RekerCancer immunotherapyImmunologyMelanomaT cellshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1BACKGROUND. Neoantigen-driven recognition and T cell–mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs). Yet how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells.Fil: Kristensen, Nikolaj Pagh. Technical University of Denmark; DinamarcaFil: Heeke, Christina. Technical University of Denmark; DinamarcaFil: Tvingsholm, Siri A.. Technical University of Denmark; DinamarcaFil: Borch, Annie. Technical University of Denmark; DinamarcaFil: Draghi, Arianna. Copenhagen University Hospital; DinamarcaFil: Crowther, Michael D.. Copenhagen University Hospital; DinamarcaFil: Carri, Ibel. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Munk, Kamilla K.. Technical University of Denmark; DinamarcaFil: Holm, Jeppe Sejerø. Technical University of Denmark; DinamarcaFil: Bjerregaard, Anne Mette. Technical University of Denmark; DinamarcaFil: Bentzen, Amalie Kai. Technical University of Denmark; DinamarcaFil: Marquard, Andrea M.. Technical University of Denmark; DinamarcaFil: Szallasi, Zoltan. Danish Cancer Society Research Center; DinamarcaFil: McGranahan, Nicholas. University College London; Estados UnidosFil: Andersen, Rikke. Copenhagen University Hospital; DinamarcaFil: Nielsen, Morten. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Jönsson, Göran B.. Faculty Of Medicine ; Lund University;Fil: Donia, Marco. Copenhagen University Hospital; DinamarcaFil: Svane, Inge Marie. Copenhagen University Hospital; DinamarcaFil: Hadrup, Sine Reker. Technical University of Denmark; DinamarcaAmerican Society for Clinical Investigation2022-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/214381Kristensen, Nikolaj Pagh; Heeke, Christina; Tvingsholm, Siri A.; Borch, Annie; Draghi, Arianna; et al.; Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma; American Society for Clinical Investigation; Journal of Clinical Investigation; 132; 2; 1-2022; 1-160021-9738CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.jci.org/articles/view/150535info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI150535info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:38Zoai:ri.conicet.gov.ar:11336/214381instacron: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:34982025-09-03 10:10:38.224CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
title Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
spellingShingle Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
Kristensen, Nikolaj Pagh
Cancer immunotherapy
Immunology
Melanoma
T cells
title_short Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
title_full Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
title_fullStr Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
title_full_unstemmed Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
title_sort Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
dc.creator.none.fl_str_mv Kristensen, Nikolaj Pagh
Heeke, Christina
Tvingsholm, Siri A.
Borch, Annie
Draghi, Arianna
Crowther, Michael D.
Carri, Ibel
Munk, Kamilla K.
Holm, Jeppe Sejerø
Bjerregaard, Anne Mette
Bentzen, Amalie Kai
Marquard, Andrea M.
Szallasi, Zoltan
McGranahan, Nicholas
Andersen, Rikke
Nielsen, Morten
Jönsson, Göran B.
Donia, Marco
Svane, Inge Marie
Hadrup, Sine Reker
author Kristensen, Nikolaj Pagh
author_facet Kristensen, Nikolaj Pagh
Heeke, Christina
Tvingsholm, Siri A.
Borch, Annie
Draghi, Arianna
Crowther, Michael D.
Carri, Ibel
Munk, Kamilla K.
Holm, Jeppe Sejerø
Bjerregaard, Anne Mette
Bentzen, Amalie Kai
Marquard, Andrea M.
Szallasi, Zoltan
McGranahan, Nicholas
Andersen, Rikke
Nielsen, Morten
Jönsson, Göran B.
Donia, Marco
Svane, Inge Marie
Hadrup, Sine Reker
author_role author
author2 Heeke, Christina
Tvingsholm, Siri A.
Borch, Annie
Draghi, Arianna
Crowther, Michael D.
Carri, Ibel
Munk, Kamilla K.
Holm, Jeppe Sejerø
Bjerregaard, Anne Mette
Bentzen, Amalie Kai
Marquard, Andrea M.
Szallasi, Zoltan
McGranahan, Nicholas
Andersen, Rikke
Nielsen, Morten
Jönsson, Göran B.
Donia, Marco
Svane, Inge Marie
Hadrup, Sine Reker
author2_role 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 Cancer immunotherapy
Immunology
Melanoma
T cells
topic Cancer immunotherapy
Immunology
Melanoma
T cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv BACKGROUND. Neoantigen-driven recognition and T cell–mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs). Yet how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells.
Fil: Kristensen, Nikolaj Pagh. Technical University of Denmark; Dinamarca
Fil: Heeke, Christina. Technical University of Denmark; Dinamarca
Fil: Tvingsholm, Siri A.. Technical University of Denmark; Dinamarca
Fil: Borch, Annie. Technical University of Denmark; Dinamarca
Fil: Draghi, Arianna. Copenhagen University Hospital; Dinamarca
Fil: Crowther, Michael D.. Copenhagen University Hospital; Dinamarca
Fil: Carri, Ibel. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Munk, Kamilla K.. Technical University of Denmark; Dinamarca
Fil: Holm, Jeppe Sejerø. Technical University of Denmark; Dinamarca
Fil: Bjerregaard, Anne Mette. Technical University of Denmark; Dinamarca
Fil: Bentzen, Amalie Kai. Technical University of Denmark; Dinamarca
Fil: Marquard, Andrea M.. Technical University of Denmark; Dinamarca
Fil: Szallasi, Zoltan. Danish Cancer Society Research Center; Dinamarca
Fil: McGranahan, Nicholas. University College London; Estados Unidos
Fil: Andersen, Rikke. Copenhagen University Hospital; Dinamarca
Fil: Nielsen, Morten. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Jönsson, Göran B.. Faculty Of Medicine ; Lund University;
Fil: Donia, Marco. Copenhagen University Hospital; Dinamarca
Fil: Svane, Inge Marie. Copenhagen University Hospital; Dinamarca
Fil: Hadrup, Sine Reker. Technical University of Denmark; Dinamarca
description BACKGROUND. Neoantigen-driven recognition and T cell–mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs). Yet how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells.
publishDate 2022
dc.date.none.fl_str_mv 2022-01
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
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/214381
Kristensen, Nikolaj Pagh; Heeke, Christina; Tvingsholm, Siri A.; Borch, Annie; Draghi, Arianna; et al.; Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma; American Society for Clinical Investigation; Journal of Clinical Investigation; 132; 2; 1-2022; 1-16
0021-9738
CONICET Digital
CONICET
url http://hdl.handle.net/11336/214381
identifier_str_mv Kristensen, Nikolaj Pagh; Heeke, Christina; Tvingsholm, Siri A.; Borch, Annie; Draghi, Arianna; et al.; Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma; American Society for Clinical Investigation; Journal of Clinical Investigation; 132; 2; 1-2022; 1-16
0021-9738
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.jci.org/articles/view/150535
info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI150535
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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