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Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma

BACKGROUND: Programmed cell death 1 (PD1) inhibitors have recently shown promising anti-cancer effects in a number of solid tumor types. A predictive biomarker to this class of drugs has not been clearly identified; however, overexpression of the PD1 ligand (PD-L1) has shown particular promise in lu...

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Autores principales: Tessier-Cloutier, Basile, Kalloger, Steve E., Al-Kandari, Mohammad, Milne, Katy, Gao, Dongxia, Nelson, Brad H., Renouf, Daniel J., Sheffield, Brandon S., Schaeffer, David F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584324/
https://www.ncbi.nlm.nih.gov/pubmed/28870260
http://dx.doi.org/10.1186/s12885-017-3634-5
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author Tessier-Cloutier, Basile
Kalloger, Steve E.
Al-Kandari, Mohammad
Milne, Katy
Gao, Dongxia
Nelson, Brad H.
Renouf, Daniel J.
Sheffield, Brandon S.
Schaeffer, David F.
author_facet Tessier-Cloutier, Basile
Kalloger, Steve E.
Al-Kandari, Mohammad
Milne, Katy
Gao, Dongxia
Nelson, Brad H.
Renouf, Daniel J.
Sheffield, Brandon S.
Schaeffer, David F.
author_sort Tessier-Cloutier, Basile
collection PubMed
description BACKGROUND: Programmed cell death 1 (PD1) inhibitors have recently shown promising anti-cancer effects in a number of solid tumor types. A predictive biomarker to this class of drugs has not been clearly identified; however, overexpression of the PD1 ligand (PD-L1) has shown particular promise in lung adenocarcinoma. In this study, we explore the staining characteristics, prevalence, and clinico-molecular correlates of PD-L1 overexpression in pancreatic ductal adenocarcinoma (PDAC). METHODS: A tissue microarray (TMA) was constructed from cases of resected PDAC. PD-L1 immunohistochemistry (IHC) was performed using the SP142 primary antibody. Immunohistochemical assessment for deficient mismatch repair status (MMRd), CD3 and CD8 were performed. All biomarkers were assessed independently by two anatomical pathologists and consensus achieved on all cases. Survival analysis was performed using three thresholds (> = 1%, >5% and >10%) for tumor cell membrane staining. RESULTS: Two-hundred fifty-two cases were included in the TMA and evaluable by IHC. Thirty-one (12%), 17 (7%), 12(5%) cases were positive at percentage cut offs of >0, >5, and >10% respectively. Increased PD-L1 expression was associated with inferior prognosis (p = 0.0367). No statistically significant association was identified between PD-L1 status and MMR status or tumor infiltrating lymphocytes. CONCLUSIONS: This data suggests that there is an inverse relationship between PD-L1 expression and disease specific survival times in resected PDAC. Consequently, this association may represent a phenotype where increased PD-L1 expression has an effect on tumor biology and could therefore identify a subgroup where PD1 blockade could have enhanced effectiveness.
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spelling pubmed-55843242017-09-06 Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma Tessier-Cloutier, Basile Kalloger, Steve E. Al-Kandari, Mohammad Milne, Katy Gao, Dongxia Nelson, Brad H. Renouf, Daniel J. Sheffield, Brandon S. Schaeffer, David F. BMC Cancer Research Article BACKGROUND: Programmed cell death 1 (PD1) inhibitors have recently shown promising anti-cancer effects in a number of solid tumor types. A predictive biomarker to this class of drugs has not been clearly identified; however, overexpression of the PD1 ligand (PD-L1) has shown particular promise in lung adenocarcinoma. In this study, we explore the staining characteristics, prevalence, and clinico-molecular correlates of PD-L1 overexpression in pancreatic ductal adenocarcinoma (PDAC). METHODS: A tissue microarray (TMA) was constructed from cases of resected PDAC. PD-L1 immunohistochemistry (IHC) was performed using the SP142 primary antibody. Immunohistochemical assessment for deficient mismatch repair status (MMRd), CD3 and CD8 were performed. All biomarkers were assessed independently by two anatomical pathologists and consensus achieved on all cases. Survival analysis was performed using three thresholds (> = 1%, >5% and >10%) for tumor cell membrane staining. RESULTS: Two-hundred fifty-two cases were included in the TMA and evaluable by IHC. Thirty-one (12%), 17 (7%), 12(5%) cases were positive at percentage cut offs of >0, >5, and >10% respectively. Increased PD-L1 expression was associated with inferior prognosis (p = 0.0367). No statistically significant association was identified between PD-L1 status and MMR status or tumor infiltrating lymphocytes. CONCLUSIONS: This data suggests that there is an inverse relationship between PD-L1 expression and disease specific survival times in resected PDAC. Consequently, this association may represent a phenotype where increased PD-L1 expression has an effect on tumor biology and could therefore identify a subgroup where PD1 blockade could have enhanced effectiveness. BioMed Central 2017-09-05 /pmc/articles/PMC5584324/ /pubmed/28870260 http://dx.doi.org/10.1186/s12885-017-3634-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Tessier-Cloutier, Basile
Kalloger, Steve E.
Al-Kandari, Mohammad
Milne, Katy
Gao, Dongxia
Nelson, Brad H.
Renouf, Daniel J.
Sheffield, Brandon S.
Schaeffer, David F.
Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma
title Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma
title_full Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma
title_fullStr Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma
title_full_unstemmed Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma
title_short Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma
title_sort programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584324/
https://www.ncbi.nlm.nih.gov/pubmed/28870260
http://dx.doi.org/10.1186/s12885-017-3634-5
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