Journal of Immunology Research (Jan 2020)

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

  • Heike Loeser,
  • Max Kraemer,
  • Florian Gebauer,
  • Christiane Bruns,
  • Wolfgang Schröder,
  • Thomas Zander,
  • Hakan Alakus,
  • Arnulf Hoelscher,
  • Reinhard Buettner,
  • Philipp Lohneis,
  • Alexander Quaas

Journal volume & issue
Vol. 2020


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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.