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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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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. |
format | Online Article Text |
id | pubmed-5620140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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