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

Ari J. Rosenberg, Derek A. Wainwright, Alfred Rademaker, Carlos Galvez, Matthew Genet, Lijie Zhai, Kristen L. Lauing, Mary F. Mulcahy, John P. Hayes, David D. Odell, Craig Horbinski, Srinadh Komanduri, Marie Pier Tetreault, Kwang Youn A. Kim, Victoria M. Villaflor*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 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

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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 A.} and Alfred Rademaker and Carlos Galvez and Matthew Genet and Lijie Zhai and Lauing, {Kristen L.} and Mulcahy, {Mary F.} and Hayes, {John P.} and Odell, {David D.} and Craig Horbinski and Srinadh Komanduri and Tetreault, {Marie Pier} and Kim, {Kwang Youn A.} and Villaflor, {Victoria M.}",
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 A.

AU - Rademaker, Alfred

AU - Galvez, Carlos

AU - Genet, Matthew

AU - Zhai, Lijie

AU - Lauing, Kristen L.

AU - Mulcahy, Mary F.

AU - Hayes, John P.

AU - Odell, David D.

AU - Horbinski, Craig

AU - Komanduri, Srinadh

AU - Tetreault, Marie Pier

AU - Kim, Kwang Youn A.

AU - Villaflor, Victoria M.

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

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U2 - 10.18632/oncotarget.25235

DO - 10.18632/oncotarget.25235

M3 - Article

C2 - 29805749

AN - SCOPUS:85046819292

VL - 9

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JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

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