Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC).
PD-L1
cellsearch
circulating tumor cells
immune checkpoint inhibition
urothelial carcinoma
vimentin
Journal
Oncoimmunology
ISSN: 2162-4011
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
2020
2020
Historique:
received:
11
09
2019
revised:
29
10
2019
accepted:
18
01
2020
entrez:
12
5
2020
pubmed:
12
5
2020
medline:
12
5
2020
Statut:
epublish
Résumé
Immune checkpoint inhibition (ICI) of the PD-1/PD-L1 axis shows durable responses in a subset of patients with metastatic urothelial carcinoma (UC). However, PD-L1 expression in tumor biopsies does not necessarily correlate with response to PD-1/PD-L1 inhibitors. Thus, a reliable predictive biomarker is urgently needed. Here, the expression of PD-L1 on circulating tumor cells (CTCs) in blood from patients with advanced UC was analyzed. For this purpose, an assay to test PD-L1 expression on CTCs using the CellSearch® system was established using cells of five UC cell lines spiked into blood samples from healthy donors and applied to a heterogeneous cohort of UC patients. Enumeration of CTCs was performed in blood samples from 49 patients with advanced UC. PD-L1 expression in ≥1 CTC was found in 10 of 16 CTC-positive samples (63%). Both intra- and inter-patient heterogeneity regarding PD-L1 expression of CTCs were observed. Furthermore, vimentin-expressing CTCs were detected in 4 of 15 CTC-positive samples (27%), independently of PD-L1 analysis. Both CTC detection and presence of CTCs with moderate or strong PD-L1 expression correlated with worse overall survival. Analyses during disease course of three individual patients receiving ICI suggest that apart from CTC numbers also PD-L1 expression on CTCs might potentially indicate disease progression. This is the first study demonstrating the feasibility to detect CTC-PD-L1 expression in patients with advanced UC using the CellSearch® system. This assay is readily available for clinical application and could be implemented in future clinical trials to evaluate its relevance for predicting and monitoring response to ICI.
Identifiants
pubmed: 32391189
doi: 10.1080/2162402X.2020.1738798
pii: 1738798
pmc: PMC7199812
doi:
Substances chimiques
B7-H1 Antigen
0
Vimentin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
1738798Informations de copyright
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
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