Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Oncol Rep. 2018 Oct;40(4):2115-2126. doi: 10.3892/or.2018.6627. Epub 2018 Aug 6.
The T‑cell immunoglobulin and mucin domain‑containing protein 3 (Tim‑3)/galectin 9 (Gal‑9) pathway, which serves a pivotal role in immune regulation, is similar to the programmed death (PD)‑1/PD‑ligand 1 pathway. Recent evidence has suggested that Tim‑3 is differentially regulated in a variety of tumors and is a potential therapeutic target. The aim of the present study was to evaluate Tim‑3 and Gal‑9 expression and cluster of differentiation (CD)3+, CD8+ and forkhead box (FOX)p3+ T cell tumor‑infiltration in gastric cancer, as well as their impact on prognosis. Tissue samples from 587 patients with gastric cancer were used to create a tissue microarray (TMA). The immune markers Tim‑3, Gal‑9, CD3, CD8 and FOXp3 were immunostained in the TMA, and correlations with clinicopathological findings and prognosis were analyzed. Several Gene Expression Omnibus gastric cancer databases and the K‑M plotter website were used to analyze the association between the expression of Tim‑3, Gal‑9 and CD8A RNA and patient survival. The results demonstrated that Tim‑3 was mainly expressed in immune cells, with minimal expression in gastric cancer cells. Its ligand, Gal‑9, was significantly overexpressed in tumor cells. Tim‑3 and Gal‑9 expression and Foxp3+ T cell density were negatively associated with the patient overall survival (OS) rate. The density of CD8+ T cells was positively associated with the patient OS rate. Tim‑3 expression and CD8+ T cell density were revealed to be independent prognostic factors for patients with gastric cancer.
T 细胞免疫球蛋白和粘蛋白结构域蛋白 3(Tim-3)/半乳糖凝集素 9(Gal-9)途径在免疫调节中起着关键作用,类似于程序性死亡(PD)-1/PD-配体 1 途径。最近的证据表明,Tim-3 在多种肿瘤中受到差异调控,是潜在的治疗靶点。本研究旨在评估胃癌中 Tim-3 和 Gal-9 表达以及 CD3+、CD8+和叉头框(FOX)p3+T 细胞肿瘤浸润,并分析其对预后的影响。使用 587 例胃癌患者的组织样本制作组织微阵列(TMA)。在 TMA 中对免疫标志物 Tim-3、Gal-9、CD3、CD8 和 FOXp3 进行免疫染色,并分析与临床病理发现和预后的相关性。使用几个基因表达综合(GEO)胃癌数据库和 K-M plotter 网站分析 Tim-3、Gal-9 和 CD8A RNA 表达与患者生存之间的关联。结果表明,Tim-3 主要在免疫细胞中表达,在胃癌细胞中表达较少。其配体 Gal-9 在肿瘤细胞中显著过表达。Tim-3 和 Gal-9 表达以及 Foxp3+T 细胞密度与患者总生存率(OS)率呈负相关。CD8+T 细胞密度与患者 OS 率呈正相关。Tim-3 表达和 CD8+T 细胞密度被揭示为胃癌患者的独立预后因素。