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dc.contributor.authorPeña Asensio, Julia 
dc.contributor.authorCalvo Sánchez, Henar
dc.contributor.authorTorralba González de Suso, Miguel 
dc.contributor.authorMiquel Plaza, Joaquín
dc.contributor.authorSanz de Villalobos, Eduardo
dc.contributor.authorLarrubia Marfil, Juan Ramón 
dc.date.accessioned2022-03-01T09:17:43Z
dc.date.available2022-03-01T09:17:43Z
dc.date.issued2021-04-16
dc.identifier.bibliographicCitationCancers, 2021, v. 13, n. 8, p. 1922en
dc.identifier.issn2072-6694
dc.identifier.urihttp://hdl.handle.net/10017/50894
dc.descriptionPeña-Asensio, J.; Calvo, H.; Torralba, M.; Miquel, J.; Sanz-de-Villalobos, E.; Larrubia, J.-R. Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma. Cancers 2021, 13, 1922.en
dc.description.abstractThirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens or aberrantly expressed host’s antigens, but they become progressively exhausted or deleted. These cells express the negative immunoregulatory checkpoint programmed cell death protein 1 (PD-1) which impairs T cell receptor signaling by blocking the CD28 positive co-stimulatory signal. The pool of CD8 cells sensitive to anti-PD-1/PD-L1 treatment is the PD-1dim memory-like precursor pool that gives rise to the effector subset involved in HCC control. Due to the epigenetic imprints that are transmitted to the next generation, the effect of PD-1 blockade is transient, and repeated treatments lead to tumor resistance. During long-lasting disease, besides the TCR signaling impairment, T cells develop other failures that should be also set-up to increase T cell reactivity. Therefore, several PD-1 blockade-based combinatory therapies are currently under investigation such as adding antiangiogenics, anti-TGFβ1, blockade of other negative immune checkpoints, or increasing HCC antigen presentation. The effect of these combinations on CD8+ T cells is discussed in this review.en
dc.description.sponsorshipInstituto de Salud Carlos IIIes
dc.description.sponsorshipEuropean Regional Development Fund (ERDF)en
dc.description.sponsorshipEuropean Unionen
dc.description.sponsorshipGilead Fellowship Programmeen
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.rights© 2021 by the authors. Licensee MDPIen
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectHepatocellular carcinomaen
dc.subjectImmunotherapyen
dc.subjectPD-1en
dc.subjectPD-L1en
dc.subjectImmune check-point inhibitoren
dc.subjectCombination therapyen
dc.subjectCD8 T cell responseen
dc.titleAnti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma.en
dc.typeinfo:eu-repo/semantics/articleen
dc.subject.ecienciaMedicinaes
dc.subject.ecienciaMedicinees
dc.contributor.affiliationUniversidad de Alcalá. Departamento de Medicina y Especialidades Médicases
dc.date.updated2022-03-01T09:06:31Z
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.identifier.doi10.3390/cancers13081922
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/ PI19%2F00206/ES/es
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gilead Sciences/ Gilead Fellowship Program in HIV & Hepatitis/ GLD14%2F00217 (JRL)/ES/en
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gilead Sciences/ Gilead Fellowship Program in HIV & Hepatitis/ GLD16/00014 (JRL)/ES/en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.identifier.uxxiAR/0000040467
dc.identifier.publicationtitleCancersen
dc.identifier.publicationvolume13
dc.identifier.publicationissue8
dc.identifier.publicationfirstpage1922


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