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

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.