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, ) with emphasis on early tumor stages (pT1/2: 142.1 vs. 37.1 months, ). 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.

中文翻译：

---

吲哚胺 2,3-双加氧酶 (IDO) 表达是食管腺癌的独立预后标志物

背景。吲哚胺 2,3-双加氧酶 (IDO) 是一种干扰素诱导的免疫检查点，在肿瘤浸润淋巴细胞 (TIL) 上表达。IDO 被认为是食管鳞状细胞癌的不良预后标志物，而对乳腺癌显示出积极的效果。缺少对明确定义的食管腺癌 (EAC) 队列中 IDO 表达的全面分析。方法。我们使用单蛋白和多重免疫组织化学以及 mRNA 原位技术分析了 551 名 EAC 患者，以了解 IDO 在 TIL 亚型（INF- γ mRNA 以及 CD4 和 CD8 阳性 T 淋巴细胞）上的表达和分布。结果。在高达 59.6% 的肿瘤中观察到 TIL 上的 IDO 表达，在肿瘤细胞中观察到 IDO 表达的比例为 9.2%。我们发现EAC 肿瘤微环境中IDO 阳性 TIL、CD3 阳性 T 淋巴细胞和产生 INF- γ mRNA 的 TIL 呈强正相关，显示出显着更好的总生存期（47.7 个月与 22.7 个月，）重点关注早期肿瘤阶段（pT1/2：142.1 个月与 37.1 个月，）。在多变量分析中，IDO 被确定为独立的预后标志物。结论。我们的研究强调了免疫调节在 EAC 中的重要性，将 IDO 标记为潜在的生物标志物。除此之外，IDO 可能表明 EAC 的一个亚组具有明确的生存益处。