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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorCalvet-Mirabent, Marta
dc.contributor.authorSanchez-Cerrillo, Ildefonso
dc.contributor.authorMartin-Cofreces, Noa B
dc.contributor.authorMartínez-Fleta, Pedro
dc.contributor.authorde la Fuente, Hortensia
dc.contributor.authorTsukalov, Ilya
dc.contributor.authorBuzón Gómez, María José
dc.date.accessioned2022-09-09T08:44:16Z
dc.date.available2022-09-09T08:44:16Z
dc.date.issued2022-07
dc.identifier.citationCalvet-Mirabent M, Sánchez-Cerrillo I, Martín-Cófreces N, Martínez-Fleta P, de la Fuente H, Tsukalov I, et al. Antiretroviral therapy duration and immunometabolic state determine efficacy of ex vivo dendritic cell-based treatment restoring functional HIV-specific CD8+ T cells in people living with HIV. eBioMedicine. 2022 Jul;81:104090.
dc.identifier.issn2352-3964
dc.identifier.urihttp://hdl.handle.net/11351/8101
dc.descriptionHIV; Immunotherapy; Metabolism
dc.description.abstractBackground Dysfunction of CD8+ T cells in people living with HIV-1 (PLWH) receiving anti-retroviral therapy (ART) has restricted the efficacy of dendritic cell (DC)-based immunotherapies against HIV-1. Heterogeneous immune exhaustion and metabolic states of CD8+ T cells might differentially associate with dysfunction. However, specific parameters associated to functional restoration of CD8+ T cells after DC treatment have not been investigated. Methods We studied association of restoration of functional HIV-1-specific CD8+ T cell responses after stimulation with Gag-adjuvant-primed DC with ART duration, exhaustion, metabolic and memory cell subsets profiles. Findings HIV-1-specific CD8+ T cell responses from a larger proportion of PLWH on long-term ART (more than 10 years; LT-ARTp) improved polyfunctionality and capacity to eliminate autologous p24+ infected CD4+ T cells in vitro. In contrast, functional improvement of CD8+ T cells from PLWH on short-term ART (less than a decade; ST-ARTp) after DC treatment was limited. This was associated with lower frequencies of central memory CD8+ T cells, increased co-expression of PD1 and TIGIT and reduced mitochondrial respiration and glycolysis induction upon TCR activation. In contrast, CD8+ T cells from LT-ARTp showed increased frequencies of TIM3+ PD1− cells and preserved induction of glycolysis. Treatment of dysfunctional CD8+ T cells from ST-ARTp with combined anti-PD1 and anti-TIGIT antibodies plus a glycolysis promoting drug restored their ability to eliminate infected CD4+ T cells. Interpretation Together, our study identifies specific immunometabolic parameters for different PLWH subgroups potentially useful for future personalized DC-based HIV-1 vaccines.
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofserieseBioMedicine;81
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectInfeccions per VIH - Tractament
dc.subjectAntiretrovirals - Ús terapèutic
dc.subjectCèl·lules dendrítiques
dc.subject.meshDendritic Cells
dc.subject.meshHIV Infections
dc.subject.mesh/drug therapy
dc.subject.meshAnti-Retroviral Agents
dc.titleAntiretroviral therapy duration and immunometabolic state determine efficacy of ex vivo dendritic cell-based treatment restoring functional HIV-specific CD8+ T cells in people living with HIV
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1016/j.ebiom.2022.104090
dc.subject.decscélulas dendríticas
dc.subject.decsinfecciones por VIH
dc.subject.decs/farmacoterapia
dc.subject.decsantirretrovirales
dc.relation.publishversionhttps://doi.org/10.1016/j.ebiom.2022.104090
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Calvet-Mirabent M, Sánchez-Cerrillo I] Immunology Unit from Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa, Madrid, Spain. Universidad Autónoma de Madrid, Madrid, Spain. [Martín-Cófreces N] Immunology Unit from Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa, Madrid, Spain. Universidad Autónoma de Madrid, Madrid, Spain. Centro de Investigación Biomédica en Red Cardiovascular, CIBERCV, Madrid, Spain. [Martínez-Fleta P] Immunology Unit from Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa, Madrid, Spain. [de la Fuente H] Immunology Unit from Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa, Madrid, Spain. Centro de Investigación Biomédica en Red Cardiovascular, CIBERCV, Madrid, Spain. [Tsukalov I] Universidad Autónoma de Madrid, Madrid, Spain. [Buzón MJ] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
dc.identifier.pmid35665682
dc.identifier.wos000812936000007
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/CP17%2F00179
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2017-2020/RTI2018-101082-B-100
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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