Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients

[EN] Immunotherapy has opened new avenues of treatment for patients with advanced non-small cell lung cancer (NSCLC) without previous hope of survival. Unfortunately, only a small percentage of patients benefit from it and there is not an effective biomarker to predict patients' response. S...

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Authors: Pino-Gonzalez, Manuel, Lazaro-Quintela, Martin, Alonso-Alvarez, Irene, Gallardo-Gomez, Maria, Juaneda-Magdalena, Laura, Francisco-Fernandez, Alejandro, Calabuig-Farinas, Silvia, Martinez-Fernandez, Monica, Jantus-Lewintre, Eloisa|||0000-0001-7395-4380
Format: article
Publication Date:2025
Country:España
Institution:Universitat Politècnica de València (UPV)
Repository:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Language:English
OAI Identifier:oai:dnet:riunet______::93d88b6c18f83d79f64d9b55d5eb737a
Online Access:https://riunet.upv.es/handle/10251/233693
Access Level:Open access
Keyword:Non-small cell lung cancer
Pembrolizumab
Predictive biomarker
Immunotherapy response
T cell receptor
TCR repertoire
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spelling Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patientsPino-Gonzalez, ManuelLazaro-Quintela, MartinAlonso-Alvarez, IreneGallardo-Gomez, MariaJuaneda-Magdalena, LauraFrancisco-Fernandez, AlejandroCalabuig-Farinas, SilviaMartinez-Fernandez, MonicaJantus-Lewintre, Eloisa|||0000-0001-7395-4380Non-small cell lung cancerPembrolizumabPredictive biomarkerImmunotherapy responseT cell receptorTCR repertoire[EN] Immunotherapy has opened new avenues of treatment for patients with advanced non-small cell lung cancer (NSCLC) without previous hope of survival. Unfortunately, only a small percentage of patients benefit from it and there is not an effective biomarker to predict patients' response. Since T cells are key effectors of antitumor immunity, T cell receptor (TCR) has emerged as a potential predictive biomarker. Here, we evaluated the potential of baseline TCR repertoire, as a predictive biomarker in advanced NSCLC patients treated with pembrolizumab at first-line. After obtaining peripheral blood and tissue samples at baseline, next-generation sequencing targeting TCR beta/gamma was performed. We found an uneven tumor-infiltrating TCR beta repertoire, and the use of various tumor-infiltrating and circulating TRBV/J genes were able of predicting the immunotherapy response. Our results support the potential of evaluating tissue and circulating TCR beta repertoire prior to pembrolizumab, revealing it as a promising immunotherapy response biomarker in NSCLC patients.This work was supported by the Instituto de Salud Carlos III (ISCIII) and cofunded by European Union under Grants PI21/00348 and CP20/00188. MPG is currently supported by the predoctoral fellowship from Ministerio de Ciencia, Innovacion y Universidaders (FPU23/00744) and previously supported by the Axencia Galega de Innovacion-GAIN (Xunta de Galicia) under Grant for the predoctoral stage IN606A-2024/017. MGG is currently supported by the Axencia Galega de Innovacion-GAIN (Xunta de Galicia) under Grant for the postdoctoral stage IN606B-2024/014. MMF is currently supported by the Instituto de Salud Carlos III (ISCIII) under the Miguel Servet program CP20/00188.Nature Publishing GroupDepartamento de BiotecnologíaCentro Avanzado de Microbiología AplicadaEscuela Técnica Superior de Ingeniería Agronómica y del Medio NaturalXunta de GaliciaInstituto de Salud Carlos IIIMinisterio de Ciencia, Innovación y UniversidadesRepositorio Institucional de la Universitat Politècnica de València Riunet20252025-11-20journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://riunet.upv.es/handle/10251/233693reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI21%2F00348 UNA PERSPECTIVA EPIGENETICA EN LA ERA DE LA INMUNO-ONCOLOGIAINSTITUTO DE SALUD CARLOS III INSTITUTO DE SALUD CARLOS III PI22%2F01221 Una nueva aproximación en inmunooncología de precisión: desarrollo de organoides tumorales derivados de pacientes de última generación. Hacia terapias personalizadas basadas en neoantígenosXunta de Galicia http://dx.doi.org/10.13039/501100010801 IN606A-2024%2F017Xunta de Galicia http://dx.doi.org/10.13039/501100010801 IN606B-2024%2F014Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP20%2F00188Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 FPU23%2F00744open accesshttp://purl.org/coar/access_right/c_abf2Reconocimiento - No comercial - Sin obra derivada (by-nc-nd) http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:riunet______::93d88b6c18f83d79f64d9b55d5eb737a2026-06-13T07:49:27Z
dc.title.none.fl_str_mv Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients
title Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients
spellingShingle Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients
Pino-Gonzalez, Manuel
Non-small cell lung cancer
Pembrolizumab
Predictive biomarker
Immunotherapy response
T cell receptor
TCR repertoire
title_short Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients
title_full Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients
title_fullStr Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients
title_full_unstemmed Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients
title_sort Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients
dc.creator.none.fl_str_mv Pino-Gonzalez, Manuel
Lazaro-Quintela, Martin
Alonso-Alvarez, Irene
Gallardo-Gomez, Maria
Juaneda-Magdalena, Laura
Francisco-Fernandez, Alejandro
Calabuig-Farinas, Silvia
Martinez-Fernandez, Monica
Jantus-Lewintre, Eloisa|||0000-0001-7395-4380
author Pino-Gonzalez, Manuel
author_facet Pino-Gonzalez, Manuel
Lazaro-Quintela, Martin
Alonso-Alvarez, Irene
Gallardo-Gomez, Maria
Juaneda-Magdalena, Laura
Francisco-Fernandez, Alejandro
Calabuig-Farinas, Silvia
Martinez-Fernandez, Monica
Jantus-Lewintre, Eloisa|||0000-0001-7395-4380
author_role author
author2 Lazaro-Quintela, Martin
Alonso-Alvarez, Irene
Gallardo-Gomez, Maria
Juaneda-Magdalena, Laura
Francisco-Fernandez, Alejandro
Calabuig-Farinas, Silvia
Martinez-Fernandez, Monica
Jantus-Lewintre, Eloisa|||0000-0001-7395-4380
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biotecnología
Centro Avanzado de Microbiología Aplicada
Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural
Xunta de Galicia
Instituto de Salud Carlos III
Ministerio de Ciencia, Innovación y Universidades
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Non-small cell lung cancer
Pembrolizumab
Predictive biomarker
Immunotherapy response
T cell receptor
TCR repertoire
topic Non-small cell lung cancer
Pembrolizumab
Predictive biomarker
Immunotherapy response
T cell receptor
TCR repertoire
description [EN] Immunotherapy has opened new avenues of treatment for patients with advanced non-small cell lung cancer (NSCLC) without previous hope of survival. Unfortunately, only a small percentage of patients benefit from it and there is not an effective biomarker to predict patients' response. Since T cells are key effectors of antitumor immunity, T cell receptor (TCR) has emerged as a potential predictive biomarker. Here, we evaluated the potential of baseline TCR repertoire, as a predictive biomarker in advanced NSCLC patients treated with pembrolizumab at first-line. After obtaining peripheral blood and tissue samples at baseline, next-generation sequencing targeting TCR beta/gamma was performed. We found an uneven tumor-infiltrating TCR beta repertoire, and the use of various tumor-infiltrating and circulating TRBV/J genes were able of predicting the immunotherapy response. Our results support the potential of evaluating tissue and circulating TCR beta repertoire prior to pembrolizumab, revealing it as a promising immunotherapy response biomarker in NSCLC patients.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-11-20
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://riunet.upv.es/handle/10251/233693
url https://riunet.upv.es/handle/10251/233693
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII) PI21%2F00348 UNA PERSPECTIVA EPIGENETICA EN LA ERA DE LA INMUNO-ONCOLOGIA
INSTITUTO DE SALUD CARLOS III INSTITUTO DE SALUD CARLOS III PI22%2F01221 Una nueva aproximación en inmunooncología de precisión: desarrollo de organoides tumorales derivados de pacientes de última generación. Hacia terapias personalizadas basadas en neoantígenos
Xunta de Galicia http://dx.doi.org/10.13039/501100010801 IN606A-2024%2F017
Xunta de Galicia http://dx.doi.org/10.13039/501100010801 IN606B-2024%2F014
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP20%2F00188
Ministerio de Ciencia, Innovación y Universidades https://doi.org/10.13039/100014440 FPU23%2F00744
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento - No comercial - Sin obra derivada (by-nc-nd)
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento - No comercial - Sin obra derivada (by-nc-nd)
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
instname:Universitat Politècnica de València (UPV)
instname_str Universitat Politècnica de València (UPV)
reponame_str RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
collection RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
repository.name.fl_str_mv
repository.mail.fl_str_mv
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