Programmed cell death ligand-1 (PD-L1) and CD8 expression profiling identify an immunologic subtype of pancreatic ductal adenocarcinomas with favorable survival

Research output: Contribution to journalArticle

Abstract

Immune-checkpoint therapy has failed to demonstrate meaningful clinical benefit in unselected cases of pancreatic adenocarcinoma (PDAC), but a subset of PDACs are known to upregulate pathways involved in acquired immune suppression. Further delineation of immunologic subtypes of PDAC is necessary to improve clinical trial designs and identify patients who might benefit from immune-checkpoint therapy. We used clinical survival and RNA expression data from The Cancer Genome Atlas (TCGA) to investigate the relationship between immune-modulating pathways and immune subset markers and their impact on survival in PDAC patients. Of the adaptive immune-resistance pathways, expression of PD-L1 and IDO1 was individually associated with poor survival. Although CD8 expression alone was not correlated with survival, the combination of PD-L1- and high CD8 expression identified a subtype with favorable survival. Wefurther extended these observations using an independent PDAC cohort from our institution via IHC, again observing that the PD-L1-/CD8high subtype was associated with positive prognosis. Although PDAC is regarded as a poorly immunogenic cancer type, these findings infer that T-cell infiltration in the absence of adaptive immune-resistance pathways is a feature of long-term survival in PDAC and imply the importance of developing future immunotherapeutic strategies based on data-supported biomarkers to refine patient selection.

Original languageEnglish (US)
Pages (from-to)886-895
Number of pages10
JournalCancer Immunology Research
Volume7
Issue number6
DOIs
StatePublished - Jun 1 2019

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Adenocarcinoma
Cell Death
Ligands
Survival
Biomarkers
Atlases
Patient Selection
Neoplasms
Up-Regulation
Clinical Trials
Genome
RNA
T-Lymphocytes
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

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title = "Programmed cell death ligand-1 (PD-L1) and CD8 expression profiling identify an immunologic subtype of pancreatic ductal adenocarcinomas with favorable survival",
abstract = "Immune-checkpoint therapy has failed to demonstrate meaningful clinical benefit in unselected cases of pancreatic adenocarcinoma (PDAC), but a subset of PDACs are known to upregulate pathways involved in acquired immune suppression. Further delineation of immunologic subtypes of PDAC is necessary to improve clinical trial designs and identify patients who might benefit from immune-checkpoint therapy. We used clinical survival and RNA expression data from The Cancer Genome Atlas (TCGA) to investigate the relationship between immune-modulating pathways and immune subset markers and their impact on survival in PDAC patients. Of the adaptive immune-resistance pathways, expression of PD-L1 and IDO1 was individually associated with poor survival. Although CD8 expression alone was not correlated with survival, the combination of PD-L1- and high CD8 expression identified a subtype with favorable survival. Wefurther extended these observations using an independent PDAC cohort from our institution via IHC, again observing that the PD-L1-/CD8high subtype was associated with positive prognosis. Although PDAC is regarded as a poorly immunogenic cancer type, these findings infer that T-cell infiltration in the absence of adaptive immune-resistance pathways is a feature of long-term survival in PDAC and imply the importance of developing future immunotherapeutic strategies based on data-supported biomarkers to refine patient selection.",
author = "Danilova, {Liudmila V} and Ho, {Won Jin} and Qingfeng Zhu and Teena Vithayathil and {De Jesus-Acosta}, Ana and Nilofer Azad and Daniel Laheru and Elana Fertig and Anders, {Robert A} and Elizabeth Jaffee and Mark Yarchoan",
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T1 - Programmed cell death ligand-1 (PD-L1) and CD8 expression profiling identify an immunologic subtype of pancreatic ductal adenocarcinomas with favorable survival

AU - Danilova, Liudmila V

AU - Ho, Won Jin

AU - Zhu, Qingfeng

AU - Vithayathil, Teena

AU - De Jesus-Acosta, Ana

AU - Azad, Nilofer

AU - Laheru, Daniel

AU - Fertig, Elana

AU - Anders, Robert A

AU - Jaffee, Elizabeth

AU - Yarchoan, Mark

PY - 2019/6/1

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N2 - Immune-checkpoint therapy has failed to demonstrate meaningful clinical benefit in unselected cases of pancreatic adenocarcinoma (PDAC), but a subset of PDACs are known to upregulate pathways involved in acquired immune suppression. Further delineation of immunologic subtypes of PDAC is necessary to improve clinical trial designs and identify patients who might benefit from immune-checkpoint therapy. We used clinical survival and RNA expression data from The Cancer Genome Atlas (TCGA) to investigate the relationship between immune-modulating pathways and immune subset markers and their impact on survival in PDAC patients. Of the adaptive immune-resistance pathways, expression of PD-L1 and IDO1 was individually associated with poor survival. Although CD8 expression alone was not correlated with survival, the combination of PD-L1- and high CD8 expression identified a subtype with favorable survival. Wefurther extended these observations using an independent PDAC cohort from our institution via IHC, again observing that the PD-L1-/CD8high subtype was associated with positive prognosis. Although PDAC is regarded as a poorly immunogenic cancer type, these findings infer that T-cell infiltration in the absence of adaptive immune-resistance pathways is a feature of long-term survival in PDAC and imply the importance of developing future immunotherapeutic strategies based on data-supported biomarkers to refine patient selection.

AB - Immune-checkpoint therapy has failed to demonstrate meaningful clinical benefit in unselected cases of pancreatic adenocarcinoma (PDAC), but a subset of PDACs are known to upregulate pathways involved in acquired immune suppression. Further delineation of immunologic subtypes of PDAC is necessary to improve clinical trial designs and identify patients who might benefit from immune-checkpoint therapy. We used clinical survival and RNA expression data from The Cancer Genome Atlas (TCGA) to investigate the relationship between immune-modulating pathways and immune subset markers and their impact on survival in PDAC patients. Of the adaptive immune-resistance pathways, expression of PD-L1 and IDO1 was individually associated with poor survival. Although CD8 expression alone was not correlated with survival, the combination of PD-L1- and high CD8 expression identified a subtype with favorable survival. Wefurther extended these observations using an independent PDAC cohort from our institution via IHC, again observing that the PD-L1-/CD8high subtype was associated with positive prognosis. Although PDAC is regarded as a poorly immunogenic cancer type, these findings infer that T-cell infiltration in the absence of adaptive immune-resistance pathways is a feature of long-term survival in PDAC and imply the importance of developing future immunotherapeutic strategies based on data-supported biomarkers to refine patient selection.

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