Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Eur J Cancer. 2018 Sep;101:20-29. doi: 10.1016/j.ejca.2018.06.020. Epub 2018 Jul 13.
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here, we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression.
In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry, and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis.
IDO1 was expressed in 260 patients (60.9%) at 1% cut-off and 63 patients (14.8%) at 50% cut-off. Tissues from 145 patients (34.0%) were positive for PD-L1 using the cut-off of 1%. Multivariate analysis showed that ≥1% IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-γ and transforming growth factor-β.
These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma.
吲哚胺 2,3-双加氧酶 1（IDO1）是一种免疫抑制效应物，其表达与几种癌症类型的预后相关。在这里，我们研究了肺腺癌中 IDO1 表达与患者预后和临床病理特征（包括程序性死亡配体 1（PD-L1）表达）之间的关系。
在这项研究中，通过免疫组织化学评估了来自 427 名患者的手术切除的原发性肺腺癌标本中的 IDO1 和 PD-L1 表达，通过酶联免疫吸附试验和流式细胞术评估肺腺癌细胞系中的 IDO1 和 PD-L1 蛋白表达，并通过实时逆转录聚合酶链反应分析评估信使 RNA 水平。
在 1%截断值下，260 名患者（60.9%）表达 IDO1，在 50%截断值下，63 名患者（14.8%）表达 IDO1。使用 1%截断值，145 名患者（34.0%）的组织为 PD-L1 阳性。多变量分析显示，≥1% IDO1 阳性与肿瘤分级较高、血管侵犯和 PD-L1 表达显著相关。IDO1 和 PD-L1 蛋白在 123 名患者（28.8%）中共同表达，共同表达的肿瘤表现出比一种蛋白阳性或两种蛋白均阴性的肿瘤更明显的恶性特征。在多变量分析中，IDO1 和 PD-L1 的共表达与无病生存和总生存显著缩短相关。两种蛋白均通过干扰素-γ和转化生长因子-β处理在肺腺癌细胞系中上调。
这些结果表明，IDO1 和 PD-L1 的共表达可能定义了一种侵袭性肺腺癌。
