Tumor-Infiltrating Immune Cells Are Associated With Prognosis of Gastric Cancer

Immune cells contribute to determining the prognosis of gastric cancer. However, their exact role is less clear. We determined the prognostic significance of different immune cells in intratumoral tissue ((T)), stromal tissue ((S)), and adjacent normal tissue ((N)) of 166 gastric cancer cases and their interactions, including CD3(+), CD4(+), CD8(+), CD57(+), CD68(+), CD66b(+), and Foxp3(+) cells, and established an effective prognostic nomogram based on the immune reactions. We found high densities of (T)CD3(+), (T)CD4(+), (T)CD8(+), (S)CD3(+), (S)CD4(+), (S)CD57(+), (S)CD66b(+), and (N)Foxp3(+) cells, as well as high (T)CD8(+)/(S)CD8(+) ratio, (T)CD68(+)/(S)CD68(+) ratio, (T)CD3(+)/(T)Foxp3(+) ratio, (T)CD4(+)/(T)Foxp3(+) ratio, (T)CD8(+)/(T)Foxp3(+) ratio, (S)CD3(+)/(S)Foxp3(+) ratio, and (S)CD4(+)/(S)CD8(+) ratio were associated with better survival, whereas high densities of (T)CD66b(+), (T)Foxp3(+), (S)Foxp3(+) and (N)CD66b(+) cells as well as high (T)CD57(+)/(S)CD57(+) ratio, (T)CD66b(+)/(S)CD66b(+) ratio, (S)CD8(+)/(S)Foxp3(+) ratio, and (T)Foxp3(+)/(N)Foxp3(+) ratio were associated with significantly worse outcome. Multivariate analysis indicated that tumor size, longitudinal tumor location, N stage, (T)CD68(+)/(S)CD68(+) ratio, (T)CD8(+)/(T)Foxp3(+) ratio, density of (T)Foxp3(+) cells, and (T)CD66b(+)/(S)CD66b(+) ratio were independent prognostic factors, which were all selected into the nomogram. The calibration curve for likelihood of survival demonstrated favorable consistency between predictive value of the nomogram and actual observation. The C-index (0.83, 95% CI: 0.78 to 0.87) of our nomogram for predicting prognosis was significantly higher than that of TNM staging system (0.70). Collectively, high (T)CD68(+)/(S)CD68(+) ratio and (T)CD8(+)/(T)Foxp3(+) ratio were associated with improved overall survival, whereas high density of (T)Foxp3(+) cells and (T)CD66b(+)/(S)CD66b(+) ratio demonstrated poor overall survival, which are promising independent predictors for overall survival in gastric cancer.