title: Frequent expression of PD-L1 on circulating breast cancer cells.
abstract: 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.
authors.affiliation: Laboratory of Rare Human Circulating Cells, Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, Montpellier, France; EA2415 - Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research (IURC), Montpellier University, Montpellier, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Mazel
authors.affiliation: Department of Medical Oncology, Montpellier Cancer Institute (ICM), Montpellier, France.
authors.forename: William
authors.initials: W
authors.lastname: Jacot
authors.affiliation: Department of Tumor Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Tumor Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Bartkowiak
authors.affiliation: University Medical Centre, Saint-Eloi Hospital, Department of Medical Oncology, Montpellier, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Topart
authors.affiliation: Laboratory of Rare Human Circulating Cells, Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, Montpellier, France; EA2415 - Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research (IURC), Montpellier University, Montpellier, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Cayrefourcq
authors.affiliation: INSERM UMR917, University of Rennes 1 and EFS, Rennes, France; Laboratory of Hematology, University Medical Centre Pontchaillou, Rennes, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Rossille
authors.affiliation: EA2415 - Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research (IURC), Montpellier University, Montpellier, France; Laboratory of Hormonal and Cell Biology, Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Maudelonde
authors.affiliation: INSERM UMR917, University of Rennes 1 and EFS, Rennes, France; Laboratory of Hematology, University Medical Centre Pontchaillou, Rennes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Fest
authors.affiliation: Laboratory of Rare Human Circulating Cells, Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, Montpellier, France; EA2415 - Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research (IURC), Montpellier University, Montpellier, France. Electronic address: c-panabieres@chu-montpellier.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Alix-Panabières
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000032:analysis*; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
chemical_list: D060890:B7-H1 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; C423236:CD274 protein, human
keywords: Breast cancer; Circulating tumor cells; PD-L1 expression