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
Fecha
2019Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Identificador del proyecto
Impacto
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10.3390/ijms20071631
Resumen
PD-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 ...
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PD-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 null [--]
Materias
PD-L1,
Biomarker,
Lung cancer,
Immunotherapy,
Immune checkpoint blockade
Editor
MDPI
Publicado en
International Journal of Molecular Sciences, 2019, 20 (7),1631
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
This 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'.