PD-L1 expression in systemic immune cell populations as a potential predictive biomarker of responses to PD-L1/PD-1 blockade therapy in lung cancer

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dc.contributor.authorBocanegra Gondán, Ana Isabel
dc.contributor.authorFernández Hinojal, Gonzalo
dc.contributor.authorZuazo Ibarra, Miren
dc.contributor.authorArasanz Esteban, Hugo
dc.contributor.authorGarcía Granda, María Jesús
dc.contributor.authorHernández, Carlos
dc.contributor.authorIbañez Vea, María
dc.contributor.authorHernandez Marin, Berta
dc.contributor.authorMartínez Aguillo, Maite
dc.contributor.authorLecumberri, María José
dc.contributor.authorFernández de Lascoiti, Ángela
dc.contributor.authorTeijeira, Lucía
dc.contributor.authorMorilla Ruiz, Idoia
dc.contributor.authorVera García, Ruth
dc.contributor.authorEscors Murugarren, David
dc.contributor.authorKochan, Grazyna
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderUniversidad Pública de Navarra / Nafarroako Unibertsitate Publikoaes
dc.date.accessioned2022-08-08T11:08:29Z
dc.date.available2022-08-08T11:08:29Z
dc.date.issued2019
dc.date.updated2022-08-08T11:05:11Z
dc.description.abstractPD-L1 tumor expression is a widely used biomarker for patient stratification in PD-L1/PD-1 blockade anticancer therapies, particularly for lung cancer. However, the reliability of this marker is still under debate. Moreover, PD-L1 is widely expressed by many immune cell types, and little is known on the relevance of systemic PD-L1+ cells for responses to immune checkpoint blockade. We present two clinical cases of patients with non-small cell lung cancer (NSCLC) and PD-L1-negative tumors treated with atezolizumab that showed either objective responses or progression. These patients showed major differences in the distribution of PD-L1 expression within systemic immune cells. Based on these results, an exploratory study was carried out with 32 cases of NSCLC patients undergoing PD-L1/PD-1 blockade therapies, to compare PD-L1 expression profiles and their relationships with clinical outcomes. Significant differences in the percentage of PD-L1+ CD11b+ myeloid cell populations were found between objective responders and non-responders. Patients with percentages of PD-L1+ CD11b+ cells above 30% before the start of immunotherapy showed response rates of 50%, and 70% when combined with memory CD4 T cell profiling. These findings indicate that quantification of systemic PD-L1+ myeloid cell subsets could provide a simple biomarker for patient stratification, even if biopsies are scored as PD-L1 nullen
dc.description.sponsorshipThis research was funded by Asociación Española Contra el Cáncer, grant number AECC PROYE16001ESCO; Instituto de Salud Carlos III, Spain, grant number FIS grant PI17/02119; and a 'Precipita' Crowdfunding grant (FECYT), no grant number. M.Z.-I. is supported by a scholarship from Universidad Pública de Navarra; H.A. is supported by a scholarship from AECC. C.H.S. is supported by a Roche fellowship 'Stop fuga de cerebros'.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBocanegra, A.; Fernandez-Hinojal, G.; Zuazo-Ibarra, M.; Arasanz, H.; Garcia-Granda, M.J.; Hernandez, C.; Ibañez, M.; Hernandez-Marin, B.; Martinez-Aguillo, M.; Lecumberri, M.J.; Fernandez de Lascoiti, A., Teijeira, L., Morilla, I., Vera, R.; Escors, D.; Kochan, G.. (2019). PD-L1 Expression in Systemic Immune Cell Populations as a Potential Predictive Biomarker of Responses to PD-L1/PD-1 Blockade Therapy in Lung Cancer. International Journal of Molecular Sciences. 20,7.en
dc.identifier.doi10.3390/ijms20071631
dc.identifier.issn1661-6596
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/43707
dc.language.isoengen
dc.publisherMDPIen
dc.relation.ispartofInternational Journal of Molecular Sciences, 2019, 20 (7),1631en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F02119/ES/
dc.relation.publisherversionhttps://doi.org/10.3390/ijms20071631
dc.rights© 2022 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licenseen
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectPD-L1en
dc.subjectBiomarkeren
dc.subjectLung canceren
dc.subjectImmunotherapyen
dc.subjectImmune checkpoint blockadeen
dc.titlePD-L1 expression in systemic immune cell populations as a potential predictive biomarker of responses to PD-L1/PD-1 blockade therapy in lung canceren
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication193d800d-c38c-4627-b9d8-d29435d8214c
relation.isAuthorOfPublicationf96114c2-9fc5-4886-ab9a-4804f14aa9c6
relation.isAuthorOfPublication4aab1ed0-620a-423b-912f-3592c35fc748
relation.isAuthorOfPublication.latestForDiscovery193d800d-c38c-4627-b9d8-d29435d8214c

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