Indoleamine 2,3-dioxygenase 1 and overall survival of patients diagnosed with esophageal cancer

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC. Results: High IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001). Conclusions: EC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC. Materials and Methods: mRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3e, followed by light microscopic analysis.

Original languageEnglish (US)
Pages (from-to)23482-23493
Number of pages12
JournalOncotarget
Volume9
Issue number34
DOIs
StatePublished - May 1 2018

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Esophageal Neoplasms
Survival
Ligands
Squamous Cell Carcinoma
Adenocarcinoma
Atlases
Immunohistochemistry
Genome
T-Lymphocytes
Neoplasms
Messenger RNA
Gene Expression
Light

Keywords

  • Checkpoint inhibitor
  • Esophageal cancer
  • Immunotherapy
  • Indoleamine 2,3 dioxygenase
  • The cancer genome atlas

ASJC Scopus subject areas

  • Oncology

Cite this

@article{e8d33a8957864f04b4b0746a19f7a1e5,
title = "Indoleamine 2,3-dioxygenase 1 and overall survival of patients diagnosed with esophageal cancer",
abstract = "Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC. Results: High IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001). Conclusions: EC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC. Materials and Methods: mRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3e, followed by light microscopic analysis.",
keywords = "Checkpoint inhibitor, Esophageal cancer, Immunotherapy, Indoleamine 2,3 dioxygenase, The cancer genome atlas",
author = "Rosenberg, {Ari J.} and Wainwright, {Derek Alan} and Rademaker, {Alfred W} and Carlos Galvez and Matthew Genet and Lijie Zhai and Lauing, {Kristen L.} and Mulcahy, {Mary Frances} and Hayes, {John P} and Odell, {David Duston} and Horbinski, {Craig Michael} and Srinadh Komanduri and Marie-Pier Tetreault and Kim, {Kwang-Youn A} and Villaflor, {Victoria Meucci}",
year = "2018",
month = "5",
day = "1",
doi = "10.18632/oncotarget.25235",
language = "English (US)",
volume = "9",
pages = "23482--23493",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "34",

}

TY - JOUR

T1 - Indoleamine 2,3-dioxygenase 1 and overall survival of patients diagnosed with esophageal cancer

AU - Rosenberg, Ari J.

AU - Wainwright, Derek Alan

AU - Rademaker, Alfred W

AU - Galvez, Carlos

AU - Genet, Matthew

AU - Zhai, Lijie

AU - Lauing, Kristen L.

AU - Mulcahy, Mary Frances

AU - Hayes, John P

AU - Odell, David Duston

AU - Horbinski, Craig Michael

AU - Komanduri, Srinadh

AU - Tetreault, Marie-Pier

AU - Kim, Kwang-Youn A

AU - Villaflor, Victoria Meucci

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC. Results: High IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001). Conclusions: EC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC. Materials and Methods: mRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3e, followed by light microscopic analysis.

AB - Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC. Results: High IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001). Conclusions: EC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC. Materials and Methods: mRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3e, followed by light microscopic analysis.

KW - Checkpoint inhibitor

KW - Esophageal cancer

KW - Immunotherapy

KW - Indoleamine 2,3 dioxygenase

KW - The cancer genome atlas

UR - http://www.scopus.com/inward/record.url?scp=85046819292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046819292&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.25235

DO - 10.18632/oncotarget.25235

M3 - Article

VL - 9

SP - 23482

EP - 23493

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 34

ER -