Show simple item record

dc.contributor.authorBaraibar, Iosune
dc.contributor.authorRoman, Marta
dc.contributor.authorRodríguez-Remírez, María
dc.contributor.authorLópez, Inés
dc.contributor.authorVilalta, Anna
dc.contributor.authorGuruceaga, Elisabeth
dc.contributor.authorEcay, Margarita
dc.contributor.authorCollantes, María
dc.contributor.authorLozano, Teresa
dc.contributor.authorAlignani, Diego
dc.contributor.authorPuyalto, Ander
dc.contributor.authorOliver, Ana
dc.contributor.authorOrtiz-Espinosa, Sergio
dc.contributor.authorMoreno, Haritz
dc.contributor.authorTorregrosa, María
dc.contributor.authorRolfo, Christian
dc.contributor.authorCaglevic, Christian
dc.contributor.authorGarcía-Ros, David
dc.contributor.authorVillalba-Esparza, María
dc.contributor.authorDe Andrea, Carlos
dc.contributor.authorVicent, Silvestre
dc.contributor.authorPío, Rubén
dc.contributor.authorLasarte, Juan José
dc.contributor.authorCalvo, Alfonso
dc.contributor.authorAjona, Daniel
dc.contributor.authorGil-Bazo, Ignacio
dc.date.accessioned2020-11-06T15:39:06Z
dc.date.available2020-11-06T15:39:06Z
dc.date.issued2020-10-28
dc.identifier.urihttp://hdl.handle.net/10713/14044
dc.description.abstractThe use of PD-1/PD-L1 checkpoint inhibitors in advanced NSCLC is associated with longer survival. However, many patients do not benefit from PD-1/PD-L1 blockade, largely because of immunosuppression. New immunotherapy-based combinations are under investigation in an attempt to improve outcomes. Id1 (inhibitor of differentiation 1) is involved in immunosuppression. In this study, we explored the potential synergistic effect of the combination of Id1 inhibition and pharmacological PD-L1 blockade in three different syngeneic murine KRAS-mutant lung adenocarcinoma models. TCGA analysis demonstrated a negative and statistically significant correlation between PD-L1 and Id1 expression levels. This observation was confirmed in vitro in human and murine KRAS-driven lung cancer cell lines. In vivo experiments in KRAS-mutant syngeneic and metastatic murine lung adenocarcinoma models showed that the combined blockade targeting Id1 and PD-1 was more effective than each treatment alone in terms of tumor growth impairment and overall survival improvement. Mechanistically, multiplex quantification of CD3+/CD4+/CD8+ T cells and flow cytometry analysis showed that combined therapy favors tumor infiltration by CD8+ T cells, whilst in vivo CD8+ T cell depletion led to tumor growth restoration. Co-culture assays using CD8+ cells and tumor cells showed that T cells present a higher antitumor effect when tumor cells lack Id1 expression. These findings highlight that Id1 blockade may contribute to a significant immune enhancement of antitumor efficacy of PD-1 inhibitors by increasing PD-L1 expression and harnessing tumor infiltration of CD8+ T lymphocytes.en_US
dc.description.urihttps://doi.org/10.3390/cancers12113169en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCancersen_US
dc.subjectKRAS lung adenocarcinomaen_US
dc.subjectPD-1 inhibitionen_US
dc.subjectPD-L1en_US
dc.subjectinhibitor of differentiationen_US
dc.titleId1 and PD-1 Combined Blockade Impairs Tumor Growth and Survival of -mutant Lung Cancer by Stimulating PD-L1 Expression and Tumor Infiltrating CD8 T Cells.en_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cancers12113169
dc.identifier.pmid33126649
dc.source.volume12
dc.source.issue11
dc.source.countrySwitzerland


This item appears in the following Collection(s)

Show simple item record