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Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC)

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 biomarke...

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Autores principales: Bergmann, Sonja, Coym, Anja, Ott, Leonie, Soave, Armin, Rink, Michael, Janning, Melanie, Stoupiec, Malgorzata, Coith, Cornelia, Peine, Sven, von Amsberg, Gunhild, Pantel, Klaus, Riethdorf, Sabine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199812/
https://www.ncbi.nlm.nih.gov/pubmed/32391189
http://dx.doi.org/10.1080/2162402X.2020.1738798
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author Bergmann, Sonja
Coym, Anja
Ott, Leonie
Soave, Armin
Rink, Michael
Janning, Melanie
Stoupiec, Malgorzata
Coith, Cornelia
Peine, Sven
von Amsberg, Gunhild
Pantel, Klaus
Riethdorf, Sabine
author_facet Bergmann, Sonja
Coym, Anja
Ott, Leonie
Soave, Armin
Rink, Michael
Janning, Melanie
Stoupiec, Malgorzata
Coith, Cornelia
Peine, Sven
von Amsberg, Gunhild
Pantel, Klaus
Riethdorf, Sabine
author_sort Bergmann, Sonja
collection PubMed
description 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.
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spelling pubmed-71998122020-05-08 Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC) Bergmann, Sonja Coym, Anja Ott, Leonie Soave, Armin Rink, Michael Janning, Melanie Stoupiec, Malgorzata Coith, Cornelia Peine, Sven von Amsberg, Gunhild Pantel, Klaus Riethdorf, Sabine Oncoimmunology Original Research 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. Taylor & Francis 2020-03-23 /pmc/articles/PMC7199812/ /pubmed/32391189 http://dx.doi.org/10.1080/2162402X.2020.1738798 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Bergmann, Sonja
Coym, Anja
Ott, Leonie
Soave, Armin
Rink, Michael
Janning, Melanie
Stoupiec, Malgorzata
Coith, Cornelia
Peine, Sven
von Amsberg, Gunhild
Pantel, Klaus
Riethdorf, Sabine
Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC)
title Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC)
title_full Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC)
title_fullStr Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC)
title_full_unstemmed Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC)
title_short Evaluation of PD-L1 expression on circulating tumor cells (CTCs) in patients with advanced urothelial carcinoma (UC)
title_sort evaluation of pd-l1 expression on circulating tumor cells (ctcs) in patients with advanced urothelial carcinoma (uc)
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199812/
https://www.ncbi.nlm.nih.gov/pubmed/32391189
http://dx.doi.org/10.1080/2162402X.2020.1738798
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