Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma.
Autores
Peña Asensio, Julia; Calvo Sánchez, Henar; Torralba González de Suso, Miguel; Miquel Plaza, Joaquín; Sanz de Villalobos, Eduardo; [et al.]Identificadores
Enlace permanente (URI): http://hdl.handle.net/10017/50894DOI: 10.3390/cancers13081922
ISSN: 2072-6694
Fecha de publicación
2021-04-16Patrocinadores
Instituto de Salud Carlos III
European Regional Development Fund (ERDF)
European Union
Gilead Fellowship Programme
Cita bibliográfica
Cancers, 2021, v. 13, n. 8, p. 1922
Palabras clave
Hepatocellular carcinoma
Immunotherapy
PD-1
PD-L1
Immune check-point inhibitor
Combination therapy
CD8 T cell response
Descripción
Peña-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.
Proyectos
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/ PI19%2F00206/ES/
info:eu-repo/grantAgreement/Gilead Sciences/ Gilead Fellowship Program in HIV & Hepatitis/ GLD14%2F00217 (JRL)/ES/
info:eu-repo/grantAgreement/Gilead Sciences/ Gilead Fellowship Program in HIV & Hepatitis/ GLD16/00014 (JRL)/ES/
Tipo de documento
info:eu-repo/semantics/article
Versión
info:eu-repo/semantics/publishedVersion
Derechos
© 2021 by the authors. Licensee MDPI
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Derechos de acceso
info:eu-repo/semantics/openAccess
Resumen
Thirty 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.
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Colecciones
- MEDICINA - Artículos [41]