LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors

Cruz, David; Rodríguez-Romanos, Rocío; González-Bartulos, Marta; García-Cadenas, Irene; Cámara, Rafael de la; Heras, Inmaculada; Buño, Ismael; Santos, Nazly; Lloveras, Natàlia; Velarde, Pilar; Tuset, Esperanza; Martínez, Carmen; González, Marcos; Sanz, Guillermo F.; Ferrá, Christelle; Sampol, Antonia; Coll, Rosa; Pérez-Simón, José A.; López-Jiménez, Javier; Jurado, Manuel; Gallardo, David; GvHD/Immunotherapy Working Party of the Spanish Group of Hematopoietic Transplant (GETH)

LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors

© 2023 Cruz, Rodríguez-Romanos, González-Bartulos, García-Cadenas, de la Cámara, Heras, Buño, Santos, Lloveras, Velarde, Tuset, Martínez, González, Sanz, Ferrá, Sampol, Coll, Pérez-Simón, López-Jiménez, Jurado and Gallardo. This is an open-access article distributed under the terms of the Creative C...

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Autores:	Cruz, David, Rodríguez-Romanos, Rocío, González-Bartulos, Marta, García-Cadenas, Irene, Cámara, Rafael de la, Heras, Inmaculada, Buño, Ismael, Santos, Nazly, Lloveras, Natàlia, Velarde, Pilar, Tuset, Esperanza, Martínez, Carmen, González, Marcos, Sanz, Guillermo F., Ferrá, Christelle, Sampol, Antonia, Coll, Rosa, Pérez-Simón, José A., López-Jiménez, Javier, Jurado, Manuel, Gallardo, David, GvHD/Immunotherapy Working Party of the Spanish Group of Hematopoietic Transplant (GETH)
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2023
País:	España
Institución:	Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:	DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:	oai:digital.csic.es:10261/351260
Acceso en línea:	http://hdl.handle.net/10261/351260
Access Level:	acceso abierto
Palabra clave:	LAG3: lymphocyte activation gene 3 Graft-versus-host disease Allogeneic transplant Checkpoint molecules Immune response

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spelling	LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donorsCruz, DavidRodríguez-Romanos, RocíoGonzález-Bartulos, MartaGarcía-Cadenas, IreneCámara, Rafael de laHeras, InmaculadaBuño, IsmaelSantos, NazlyLloveras, NatàliaVelarde, PilarTuset, EsperanzaMartínez, CarmenGonzález, MarcosSanz, Guillermo F.Ferrá, ChristelleSampol, AntoniaColl, RosaPérez-Simón, José A.López-Jiménez, JavierJurado, ManuelGallardo, DavidGvHD/Immunotherapy Working Party of the Spanish Group of Hematopoietic Transplant (GETH)LAG3: lymphocyte activation gene 3Graft-versus-host diseaseAllogeneic transplantCheckpoint moleculesImmune response© 2023 Cruz, Rodríguez-Romanos, González-Bartulos, García-Cadenas, de la Cámara, Heras, Buño, Santos, Lloveras, Velarde, Tuset, Martínez, González, Sanz, Ferrá, Sampol, Coll, Pérez-Simón, López-Jiménez, Jurado and Gallardo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Introduction: The association of polymorphisms in molecules involved in the immune response (checkpoint inhibitors) with the clinical outcome after allogeneic transplantation (alloHSCT) has been described. Lymphocyte Activation 3 (LAG3) is a surface protein that plays a regulatory role in immunity as an inhibitory immune checkpoint molecule.Methods: To determine its role in the alloHSCT setting, we analyzed 797 patients transplanted from HLA-identical sibling donors. The LAG3 rs870849 C>T polymorphism was genotyped in donors.Results: We detected a higher incidence of severe acute GVHD in patients transplanted from donors with TT genotype (p: 0.047, HR 1.64; 95% CI 1.01 – 2.67). Overall survival (OS) was worse for patients transplanted from donors with the rs870849 CT/TT genotype (0.020; HR, 1.44; 95% CI 1.06 – 1.96), as well as disease-free survival (DFS) (p: 0.002; HR 1.58, 95%CI: 1.18 – 2.14) and transplant-related mortality (TRM) (p< 0.001; HR: 1.88, 95% CI 1.29 – 2.74). When combining the LAG3 rs870849 and the PDCD1 rs36084323 genotypes of the donor, three genetic groups were well defined, allowing a good stratification of the risk of acute GVHD, TRM, OS and DFS.Discussion: We conclude that the LAG3 genotype of the donor may be considered in donors’ selection. As this selection may be limited in the HLA-identical sibling donor scenario, further studies exploring the impact of LAG3 genotype of the donor in unrelated transplantation are warranted.This work has been financed by grants PI17/00815 and PI20/01353, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union.Peer reviewedFrontiers MediaInstituto de Salud Carlos IIIEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/351260reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F00815info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01353The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.3389/fimmu.2023.1066393https://doi.org/10.3389/fimmu.2023.1066393Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3512602026-05-22T06:33:51Z
dc.title.none.fl_str_mv	LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title	LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
spellingShingle	LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors Cruz, David LAG3: lymphocyte activation gene 3 Graft-versus-host disease Allogeneic transplant Checkpoint molecules Immune response
title_short	LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title_full	LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title_fullStr	LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title_full_unstemmed	LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title_sort	LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
dc.creator.none.fl_str_mv	Cruz, David Rodríguez-Romanos, Rocío González-Bartulos, Marta García-Cadenas, Irene Cámara, Rafael de la Heras, Inmaculada Buño, Ismael Santos, Nazly Lloveras, Natàlia Velarde, Pilar Tuset, Esperanza Martínez, Carmen González, Marcos Sanz, Guillermo F. Ferrá, Christelle Sampol, Antonia Coll, Rosa Pérez-Simón, José A. López-Jiménez, Javier Jurado, Manuel Gallardo, David GvHD/Immunotherapy Working Party of the Spanish Group of Hematopoietic Transplant (GETH)
author	Cruz, David
author_facet	Cruz, David Rodríguez-Romanos, Rocío González-Bartulos, Marta García-Cadenas, Irene Cámara, Rafael de la Heras, Inmaculada Buño, Ismael Santos, Nazly Lloveras, Natàlia Velarde, Pilar Tuset, Esperanza Martínez, Carmen González, Marcos Sanz, Guillermo F. Ferrá, Christelle Sampol, Antonia Coll, Rosa Pérez-Simón, José A. López-Jiménez, Javier Jurado, Manuel Gallardo, David GvHD/Immunotherapy Working Party of the Spanish Group of Hematopoietic Transplant (GETH)
author_role	author
author2	Rodríguez-Romanos, Rocío González-Bartulos, Marta García-Cadenas, Irene Cámara, Rafael de la Heras, Inmaculada Buño, Ismael Santos, Nazly Lloveras, Natàlia Velarde, Pilar Tuset, Esperanza Martínez, Carmen González, Marcos Sanz, Guillermo F. Ferrá, Christelle Sampol, Antonia Coll, Rosa Pérez-Simón, José A. López-Jiménez, Javier Jurado, Manuel Gallardo, David GvHD/Immunotherapy Working Party of the Spanish Group of Hematopoietic Transplant (GETH)
author2_role	author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Instituto de Salud Carlos III European Commission Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv	LAG3: lymphocyte activation gene 3 Graft-versus-host disease Allogeneic transplant Checkpoint molecules Immune response
topic	LAG3: lymphocyte activation gene 3 Graft-versus-host disease Allogeneic transplant Checkpoint molecules Immune response
description	© 2023 Cruz, Rodríguez-Romanos, González-Bartulos, García-Cadenas, de la Cámara, Heras, Buño, Santos, Lloveras, Velarde, Tuset, Martínez, González, Sanz, Ferrá, Sampol, Coll, Pérez-Simón, López-Jiménez, Jurado and Gallardo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
publishDate	2023
dc.date.none.fl_str_mv	2023 2024 2024
dc.type.none.fl_str_mv	info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10261/351260
url	http://hdl.handle.net/10261/351260
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F00815 info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01353 The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.3389/fimmu.2023.1066393 https://doi.org/10.3389/fimmu.2023.1066393 Sí
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Frontiers Media
publisher.none.fl_str_mv	Frontiers Media
dc.source.none.fl_str_mv	reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC)
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LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors

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