Association between Tim‑3 and Gal‑9 expression and gastric cancer prognosis

Abstract

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.

Prognostic Values of TIM-3 Expression in Patients With Solid Tumors: A Meta-Analysis and Database Evaluation

“…Interestingly, subgroup analysis showed that TIM-3 overexpression on tumor cells was associated with poor OS, but the association between TIM-3 expression on TILs and OS didn't reach a statistical significance. TIM-3 was mainly expressed on immune cells with lower expression in tumor cells (9,42). It seems that the expression of TIM-3 on tumor cells has greater prognosis value, but the exact mechanism needs further investigation.…”

Multiplex profiling of peritoneal metastases from gastric adenocarcinoma identified novel targets and molecular subtypes that predict treatment response

“…The M subtype had high expression of TGF-β1, and immune checkpoint TIM-3, its ligand galectin-9, and another immune checkpoint VISTA, high proportion of monocytes, increased proportion of M2 macrophage, and enriched abundance of fibroblast in the TME, thus uncovering novel targets for immunotherapy. Although several studies have demonstrated that TIM-3, its ligand galectin-9 and VISTA are dysregulated in GAC tumour tissues and pointed their potential clinical implication,52–56 there are some limitations to these studies due to the study design and was limited to primary tumour tissues and PC cells were not included. However, our discovery on TIM-3/galectin-9 and other immune suppression molecules-VISTA and TGF-β1 were derived from a comprehensive profiling of patients’ PC samples.…”

Expression of galectin 9 mRNA in lactose maldigestion and children’s obesity

“…In the presence of lactose, Treg cells lose their ability to inhibit the secretion of IFN-γ and IL-17 (16.4 vs. 3.99 ng/ml, n=20, p<0.0001 and 0.74 vs. 0.64 ng/ml, n=15, p=0.005, respectively) [10]. Thus, there is an increase in cellular pro-inflammatory processes, as well as the induction of autoimmune diseases and delayed hypersensitivity reactions that support chronic inflammation [24] and tumor processes [25,26].…”