Decreased density of CD3+ tumor-infiltrating lymphocytes during gastric cancer progression

Background and Aim: Tumor cells escape host immunosurveillance and thus produce an advantageous environment for tumor progression. Recent studies have demonstrated that tumor-infiltrating lymphocytes (TILs) play a principal role in the immune response to tumors. However, little is understood about numerical alterations in CD3+ TILs during tumor progression in patients with gastric cancer. The present study examines the density of CD3+ TILs to elucidate their clinical significance in gastric cancer. Methods: The numbers of CD3+ TILs in 120 resected specimens from patients with gastric cancer and 27 endoscopic resected specimens from patients with gastric adenoma were immunohistochemically assessed using a CD3 polyclonal antibody. Results: The mean number of CD3+ TILs (+/- SD) in the patients with gastric cancer and adenoma was 87.5 +/- 59.8 and 379.6 +/- 128.1, respectively. Significantly more CD3+ TILs were found in specimens from patients with gastric adenoma than with gastric cancer (P < 0.0001). The numbers of CD3+ TILs significantly correlated with depth of tumor invasion, lymph node metastasis, and stage (P = 0.022, P = 0.0004, and P = 0.011, respectively). The 5-year survival rate was significantly poorer for patients with fewer CD3+ TILs (P = 0.004). Multivariate analysis selected the density of CD3+ TILs as an independent prognostic factor (P = 0.034). Conclusions: Our results demonstrated that the density of CD3+ TILs decreases during tumor progression. The density of CD3+ TILs is an immunological predictor of lymph node metastasis and disease outcome in patients with gastric cancer.