Indoleamine 2,3-Dioxygenase (IDO) Expression Is an Independent Prognostic Marker in Esophageal Adenocarcinoma

Background. Indoleamine 2,3-dioxygenase (IDO) is an interferon-inducible immune checkpoint expressed on tumor-infiltrating lymphocytes (TILs). IDO is known as a poor prognostic marker in esophageal squamous cell cancer, while a positive effect was shown for breast cancer. A comprehensive analysis of...

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Main Authors: Heike Loeser, Max Kraemer, Florian Gebauer, Christiane Bruns, Wolfgang Schröder, Thomas Zander, Hakan Alakus, Arnulf Hoelscher, Reinhard Buettner, Philipp Lohneis, Alexander Quaas
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/2862647
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author Heike Loeser
Max Kraemer
Florian Gebauer
Christiane Bruns
Wolfgang Schröder
Thomas Zander
Hakan Alakus
Arnulf Hoelscher
Reinhard Buettner
Philipp Lohneis
Alexander Quaas
author_facet Heike Loeser
Max Kraemer
Florian Gebauer
Christiane Bruns
Wolfgang Schröder
Thomas Zander
Hakan Alakus
Arnulf Hoelscher
Reinhard Buettner
Philipp Lohneis
Alexander Quaas
author_sort Heike Loeser
collection DOAJ
description Background. Indoleamine 2,3-dioxygenase (IDO) is an interferon-inducible immune checkpoint expressed on tumor-infiltrating lymphocytes (TILs). IDO is known as a poor prognostic marker in esophageal squamous cell cancer, while a positive effect was shown for breast cancer. A comprehensive analysis of IDO expression in a well-defined cohort of esophageal adenocarcinoma (EAC) is missing. Methods. We analyzed 551 patients with EAC using single-protein and multiplex immunohistochemistry as well as mRNA in situ technology for the expression and distribution of IDO on subtypes of TILs (INF-γ mRNA and CD4- and CD8-positive T lymphocytes). Results. IDO expression on TILs was seen in up to 59.6% of tumors, and expression on tumor cells was seen in 9.2%. We found a strong positive correlation of IDO-positive TILs, CD3-positive T lymphocytes, and INF-γ mRNA-producing TILs in the tumor microenvironment of EACs showing significantly better overall survival (47.7 vs. 22.7 months, p<0.001) with emphasis on early tumor stages (pT1/2: 142.1 vs. 37.1 months, p<0.001). In multivariate analysis, IDO is identified as an independent prognostic marker. Conclusions. Our study emphasizes the importance of immunomodulation in EAC marking IDO as a potential biomarker. Beyond this, IDO might indicate a subgroup of EAC with an explicit survival benefit.
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spelling doaj-art-74f7437396834a7eb8ff896b8ab2fd6e2025-02-03T05:49:54ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/28626472862647Indoleamine 2,3-Dioxygenase (IDO) Expression Is an Independent Prognostic Marker in Esophageal AdenocarcinomaHeike Loeser0Max Kraemer1Florian Gebauer2Christiane Bruns3Wolfgang Schröder4Thomas Zander5Hakan Alakus6Arnulf Hoelscher7Reinhard Buettner8Philipp Lohneis9Alexander Quaas10Institute of Pathology, University Hospital Cologne, GermanyInstitute of Pathology, University Hospital Cologne, GermanyGastrointestinal Cancer Group Cologne, Department I for Internal Medicine, Center for Integrated Oncology, University Hospital of Cologne, Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, GermanyGastrointestinal Cancer Group Cologne, Department I for Internal Medicine, Center for Integrated Oncology, University Hospital of Cologne, Cologne, GermanyGastrointestinal Cancer Group Cologne, Department I for Internal Medicine, Center for Integrated Oncology, University Hospital of Cologne, Cologne, GermanyCenter for Esophageal and Gastric Surgery, AGAPLESION Markus Krankenhaus, Frankfurt, GermanyInstitute of Pathology, University Hospital Cologne, GermanyInstitute of Pathology, University Hospital Cologne, GermanyInstitute of Pathology, University Hospital Cologne, GermanyBackground. Indoleamine 2,3-dioxygenase (IDO) is an interferon-inducible immune checkpoint expressed on tumor-infiltrating lymphocytes (TILs). IDO is known as a poor prognostic marker in esophageal squamous cell cancer, while a positive effect was shown for breast cancer. A comprehensive analysis of IDO expression in a well-defined cohort of esophageal adenocarcinoma (EAC) is missing. Methods. We analyzed 551 patients with EAC using single-protein and multiplex immunohistochemistry as well as mRNA in situ technology for the expression and distribution of IDO on subtypes of TILs (INF-γ mRNA and CD4- and CD8-positive T lymphocytes). Results. IDO expression on TILs was seen in up to 59.6% of tumors, and expression on tumor cells was seen in 9.2%. We found a strong positive correlation of IDO-positive TILs, CD3-positive T lymphocytes, and INF-γ mRNA-producing TILs in the tumor microenvironment of EACs showing significantly better overall survival (47.7 vs. 22.7 months, p<0.001) with emphasis on early tumor stages (pT1/2: 142.1 vs. 37.1 months, p<0.001). In multivariate analysis, IDO is identified as an independent prognostic marker. Conclusions. Our study emphasizes the importance of immunomodulation in EAC marking IDO as a potential biomarker. Beyond this, IDO might indicate a subgroup of EAC with an explicit survival benefit.http://dx.doi.org/10.1155/2020/2862647
spellingShingle Heike Loeser
Max Kraemer
Florian Gebauer
Christiane Bruns
Wolfgang Schröder
Thomas Zander
Hakan Alakus
Arnulf Hoelscher
Reinhard Buettner
Philipp Lohneis
Alexander Quaas
Indoleamine 2,3-Dioxygenase (IDO) Expression Is an Independent Prognostic Marker in Esophageal Adenocarcinoma
Journal of Immunology Research
title Indoleamine 2,3-Dioxygenase (IDO) Expression Is an Independent Prognostic Marker in Esophageal Adenocarcinoma
title_full Indoleamine 2,3-Dioxygenase (IDO) Expression Is an Independent Prognostic Marker in Esophageal Adenocarcinoma
title_fullStr Indoleamine 2,3-Dioxygenase (IDO) Expression Is an Independent Prognostic Marker in Esophageal Adenocarcinoma
title_full_unstemmed Indoleamine 2,3-Dioxygenase (IDO) Expression Is an Independent Prognostic Marker in Esophageal Adenocarcinoma
title_short Indoleamine 2,3-Dioxygenase (IDO) Expression Is an Independent Prognostic Marker in Esophageal Adenocarcinoma
title_sort indoleamine 2 3 dioxygenase ido expression is an independent prognostic marker in esophageal adenocarcinoma
url http://dx.doi.org/10.1155/2020/2862647
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