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

Abstract EN

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.