The Clinical Significance of Abnormal Tim-3 Expression on NK Cells from Patients with Gastric Cancer

Aim: To investigate the clinical significance of Tim-3 (T-cell immunoglobulin-and mucin-domain-containing molecule 3) expression in natural killer (NK) cells from patients with gastric cancer. Materials and methods: Sixty-two patients with gastric cancer and 32 healthy controls were recruited for this study. Tim-3 expression in peripheral blood samples was analyzed using flow cytometry. The expression pattern of Tim-3 on NK cells was also confirmed using a gastric cancer-bearing mouse model. To further investigate the mechanisms that regulate Tim-3 expression, T-bet(-/-), Eomes(-/-), and Eomes/T-bet double knockout mice were utilized. Additionally, we statistically analyzed the clinical significance of Tim-3 expression on NK cells. Results: We found that the levels of Tim-3 in NK cells obtained from patients with gastric cancer were significantly higher than the levels in healthy controls. Clinical analyses showed that Tim-3 levels on NK cells were associated with advanced tumor stage. In a tumor-bearing mouse model, Tim-3 levels in NK cells increased with tumor growth, indicating that tumor progression could induce Tim-3 expression in NK cells. Finally, we report that T-bet is a key factor involved in regulating Tim-3 expression. Conclusion: Our data indicate that Tim-3 expression on NK cells is regulated by T-bet, and that Tim-3 levels correlate with advanced stages of gastric cancer.