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dc.creatorLlopiz, D. (Diana)-
dc.creatorRuiz, M. (Marta)-
dc.creatorVillanueva, L. (Lorea)-
dc.creatorIglesias-Alonso, T. (Tamara)-
dc.creatorSilva, L. (Leyre)-
dc.creatorEgea, J. (Josune)-
dc.creatorLasarte, J.J. (Juan José)-
dc.creatorPerrine, P. (Perrine)-
dc.creatorTrochon-Joseph, V. (Véronique)-
dc.creatorVasseur, B. (Bérangère)-
dc.creatorDixon, G. (Graham)-
dc.creatorSangro, B. (Bruno)-
dc.creatorSarobe, P. (Pablo)-
dc.identifier.citationLlopiz, D. (Diana); Ruiz, M. (Marta); Villanueva, L. (Lorea); et al. "Enhanced anti-tumor efficacy of checkpoint inhibitors in combination with the histone deacetylase inhibitor Belinostat in a murine hepatocellular carcinoma model". Cancer immunology, immunotherapy. 68 (3), 2019, 379 - 393es
dc.description.abstractImmune checkpoint inhibitors are currently tested in different combinations in patients with advanced hepatocellular carcinoma (HCC). Nivolumab, an anti-PD-1 agent, has gained approval in the second-line setting in the USA. Epigenetic drugs have immune-mediated antitumor effects that may improve the activity of immunotherapy agents. Our aim was to study the therapeutic efficacy of checkpoint inhibitors (anti-CTLA-4 and anti-PD-1 antibodies) in combination with the histone deacetylase inhibitor (HDACi) Belinostat. In a subcutaneous Hepa129 murine HCC model, we demonstrated that Belinostat improves the antitumor activity of anti-CTLA-4 but not of anti-PD-1 therapy. This effect correlated with enhanced IFN-γ production by antitumor T-cells and a decrease in regulatory T-cells. Moreover, the combination induced early upregulation of PD-L1 on tumor antigen-presenting cells and late expression of PD-1 on tumor-infiltrating effector T-cells, suggesting the suitability of PD-1 blockade. Indeed, Belinostat combined with the simultaneous blockade of CTLA-4 and PD-1 led to complete tumor rejection. These results provide a rationale for testing Belinostat in combination with checkpoint inhibitors to enhance their therapeutic activity in patients with HCC.es_ES
dc.subjectCheckpoint inhibitorses_ES
dc.subjectHDAC inhibitores_ES
dc.subjectHepatocellular carcinomaes_ES
dc.subjectM1 macrophageses_ES
dc.subjectPD-1/PD-L1 expressiones_ES
dc.subjectT regulatory cellses_ES
dc.titleEnhanced anti-tumor efficacy of checkpoint inhibitors in combination with the histone deacetylase inhibitor Belinostat in a murine hepatocellular carcinoma modeles_ES
dadun.citation.publicationNameCancer immunology, immunotherapyes_ES

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