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Frequent expression of PD-L1 on circulating breast cancer cells

Authors :
Thierry Fest
Delphine Topart
Catherine Alix-Panabières
Thierry Maudelonde
Martine Mazel
Kai Bartkowiak
Laure Cayrefourcq
Klaus Pantel
William Jacot
Delphine Rossille
Jonchère, Laurent
Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP)
Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Laboratoire cellules circulantes rares humaines
Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier)
Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM)
CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Institute of Tumor Biology
Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE)
Département d'oncologie médicale
Laboratoire d'Hematologie
CHU Pontchaillou [Rennes]
Modélisation Conceptuelle des Connaissances Biomédicales
Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Microenvironnement et cancer (MiCa)
Laboratoire de Biologie cellulaire et Hormonale
Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve
The authors thank Delphine Gueroult for her excellent technical assistance for the CTC detection using the CellSearch® system.This work was supported by the University Medical Centre of Rennes (Internal institution support in 2013), an ANR-Roche SAS grant (TF), the FEDER and the Region Languedoc-Roussillon (GEPETOS project, N° 38 582) (CAP), the Kastner Foundation (KP) and the European Research Council Advanced Investigator grant 269081 DISSECT (KP).
Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi
Université de Rennes 1 (UR1)
Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1)
Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Source :
Molecular Oncology, Molecular Oncology, 2015, 9 (9), pp.1773-1782. ⟨10.1016/j.molonc.2015.05.009⟩, Molecular Oncology, Elsevier, 2015, 9 (9), pp.1773-1782. ⟨10.1016/j.molonc.2015.05.009⟩
Publication Year :
2015
Publisher :
HAL CCSD, 2015.

Abstract

International audience; Immune checkpoint regulators such as PD-L1 have become exciting new therapeutic targets leading to long lasting remissions in patients with advanced malignancies. However, in view of the remarkable costs and the toxicity profiles of these therapies, predictive biomarkers able to discriminate responders from non-responders are urgently needed. In the present paper, we provide evidence that PD-L1 is frequently expressed on metastatic cells circulating in the blood of hormone receptor-positive, HER2-negative breast cancer patients. We performed western blot, flow cytometry and immunocytochemical analyses to demonstrate the specificity of the PDL1 antibody used in our study and established immunoscores for PDL1 expression on single tumor cells. We then selected sixteen patients with circulating tumor cells (CTCs) using the CellSearch® system and found PD-L1(+) CTCs in 11 patients (68.8%). The fraction of PD-L1(+) CTCs varied from 0.2 to 100% in individual patients. This is the first report demonstrating the expression of PD-L1 on CTCs. The established CTC/PD-L1 assay can be used for liquid biopsy in future clinical trials for stratification and monitoring of cancer patients undergoing immune checkpoint blockade

Details

Language :
English
ISSN :
15747891 and 18780261
Database :
OpenAIRE
Journal :
Molecular Oncology, Molecular Oncology, 2015, 9 (9), pp.1773-1782. ⟨10.1016/j.molonc.2015.05.009⟩, Molecular Oncology, Elsevier, 2015, 9 (9), pp.1773-1782. ⟨10.1016/j.molonc.2015.05.009⟩
Accession number :
edsair.doi.dedup.....131ac6d9355a86bf2622e6f33f3cdfa7
Full Text :
https://doi.org/10.1016/j.molonc.2015.05.009⟩