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

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dc.contributor.authorTessier-Cloutier, Basile
dc.contributor.authorKalloger, Steve E.
dc.contributor.authorAl-Kandari, Mohammad
dc.contributor.authorMilne, Katy
dc.contributor.authorGao, Dongxia
dc.contributor.authorNelson, Brad H.
dc.contributor.authorRenouf, Daniel J.
dc.contributor.authorSheffield, Brandon S.
dc.contributor.authorSchaeffer, David F.
dc.date.accessioned2019-01-24T17:46:18Z
dc.date.available2019-01-24T17:46:18Z
dc.date.copyright2017en_US
dc.date.issued2017
dc.description.abstractBackground: 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.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis work was supported through unrestricted research funds provided by the VGH and UBC Hospital Foundation and the BC Cancer Foundation which were administered through the Pancreas Centre BC. The above funders of this research had no influence upon the design of the study, collection, analysis nor interpretation of the data or writing of the manuscript.en_US
dc.identifier.citationTessier-Cloutier, B.; Kalloger, S. E.; Al-Kandari, M.; Milne, K.; Gao, D.; Nelson, B. H.; … & Schaeffer, D. F. (2017). Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma. BMC Cancer, 17(618). DOI: 10.1186/s12885-017-3634-5en_US
dc.identifier.urihttps://doi.org/10.1186/s12885-017-3634-5
dc.identifier.urihttp://hdl.handle.net/1828/10535
dc.language.isoenen_US
dc.publisherBMC Canceren_US
dc.subjectpancreatic cancer
dc.subjectprogrammed cell death 1 ligand
dc.subjectDNA mismatch repair
dc.subjecttumor-infiltrating lymphocytes
dc.subjectbiomarkers
dc.subjectimmuno-oncology
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.titleProgrammed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinomaen_US
dc.typeArticleen_US

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