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PD-L1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy

Platinum-based chemotherapy is the standard of care in metastatic bladder cancer. With the approval of various checkpoint inhibitors, immunotherapy has revolutionized the traditional treatment modalities. The aim of the study was to evaluate whether PD-L1 expression on tumor cells (TCs) and tumor-in...

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Autores principales: Pichler, Renate, Heidegger, Isabel, Fritz, Josef, Danzl, Melanie, Sprung, Susanne, Zelger, Bettina, Brunner, Andrea, Pircher, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620140/
https://www.ncbi.nlm.nih.gov/pubmed/28978000
http://dx.doi.org/10.18632/oncotarget.19913
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author Pichler, Renate
Heidegger, Isabel
Fritz, Josef
Danzl, Melanie
Sprung, Susanne
Zelger, Bettina
Brunner, Andrea
Pircher, Andreas
author_facet Pichler, Renate
Heidegger, Isabel
Fritz, Josef
Danzl, Melanie
Sprung, Susanne
Zelger, Bettina
Brunner, Andrea
Pircher, Andreas
author_sort Pichler, Renate
collection PubMed
description Platinum-based chemotherapy is the standard of care in metastatic bladder cancer. With the approval of various checkpoint inhibitors, immunotherapy has revolutionized the traditional treatment modalities. The aim of the study was to evaluate whether PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) can be used as biomarker to predict recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS) in bladder cancer patients after radical cystectomy (RC) developing disease recurrence followed by first-line chemotherapy. PD-L1 was measured on formalin-fixed, paraffin-embedded tissue sections of RC specimens in all patients (n=61) and in 27 matched metastatic biopsy samples by immunohistochemistry. PD-L1 expression on TCs was defined by the percentage of PD-L1 positive tumor cells (< 1%= IC0, ≥1% but <5%=IC1, ≥5 %=IC2/3), and was considered negative or positive for ICs. On 27 paired samples, IC1/2/3 score on TCs was homogeneous distributed with 59.3% in primary tumors and metastases, but with a high discordance rate of 44.4% of PD-L1 positivity on ICs. High PD-L1 expression (IC2/3) on TCs was more frequently seen in histologic subtypes of urothelial cancer compared to pure urothelial cancers (46.2% vs. 20.8%; p=0.002). PD-L1 expression on TCs in primary tumors (IC2/3 vs. IC0, median: 3.2 vs. 13.8 months, p=0.019) and metastatic sites (IC2/3 vs. IC0, median: 6.1 vs. 21.8 months, p=0.014) was associated with poor chemo-response, represented by significant shortened DSS. These results suggest that PD-L1 may be a potential target being involved in chemo-resistance mechanisms and poses potential for therapy stratification in the future.
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spelling pubmed-56201402017-10-03 PD-L1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy Pichler, Renate Heidegger, Isabel Fritz, Josef Danzl, Melanie Sprung, Susanne Zelger, Bettina Brunner, Andrea Pircher, Andreas Oncotarget Research Paper Platinum-based chemotherapy is the standard of care in metastatic bladder cancer. With the approval of various checkpoint inhibitors, immunotherapy has revolutionized the traditional treatment modalities. The aim of the study was to evaluate whether PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) can be used as biomarker to predict recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS) in bladder cancer patients after radical cystectomy (RC) developing disease recurrence followed by first-line chemotherapy. PD-L1 was measured on formalin-fixed, paraffin-embedded tissue sections of RC specimens in all patients (n=61) and in 27 matched metastatic biopsy samples by immunohistochemistry. PD-L1 expression on TCs was defined by the percentage of PD-L1 positive tumor cells (< 1%= IC0, ≥1% but <5%=IC1, ≥5 %=IC2/3), and was considered negative or positive for ICs. On 27 paired samples, IC1/2/3 score on TCs was homogeneous distributed with 59.3% in primary tumors and metastases, but with a high discordance rate of 44.4% of PD-L1 positivity on ICs. High PD-L1 expression (IC2/3) on TCs was more frequently seen in histologic subtypes of urothelial cancer compared to pure urothelial cancers (46.2% vs. 20.8%; p=0.002). PD-L1 expression on TCs in primary tumors (IC2/3 vs. IC0, median: 3.2 vs. 13.8 months, p=0.019) and metastatic sites (IC2/3 vs. IC0, median: 6.1 vs. 21.8 months, p=0.014) was associated with poor chemo-response, represented by significant shortened DSS. These results suggest that PD-L1 may be a potential target being involved in chemo-resistance mechanisms and poses potential for therapy stratification in the future. Impact Journals LLC 2017-08-03 /pmc/articles/PMC5620140/ /pubmed/28978000 http://dx.doi.org/10.18632/oncotarget.19913 Text en Copyright: © 2017 Pichler et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Pichler, Renate
Heidegger, Isabel
Fritz, Josef
Danzl, Melanie
Sprung, Susanne
Zelger, Bettina
Brunner, Andrea
Pircher, Andreas
PD-L1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy
title PD-L1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy
title_full PD-L1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy
title_fullStr PD-L1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy
title_full_unstemmed PD-L1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy
title_short PD-L1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy
title_sort pd-l1 expression in bladder cancer and metastasis and its influence on oncologic outcome after cystectomy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620140/
https://www.ncbi.nlm.nih.gov/pubmed/28978000
http://dx.doi.org/10.18632/oncotarget.19913
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