Expression of the Chemokine Receptor CXCR3 Correlates with Dendritic Cell Recruitment and Prognosis in Gastric Cancer

Aim: The aim of this study was to investigate whether CXCR3 expression is associated with: infiltration of dendritic cells (DCs) and CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs); various clinical features; and overall survival (OS) of patients diagnosed with gastric cancer (GC). Materials and Methods: The study included 169 GC specimens and 91 corresponding paracancerous tissues. Immunohistochemistry was conducted to determine the expression of CXCR3 and the presence of DCs and CD4+ and CD8+ TILs. Statistical analyses were done using SPSS 17.0 software. Results: CXCR3 expression in GC tissues was significantly higher than in paracancerous tissues (p<0.001). Higher CXCR3 expression was associated with increased DC and both CD8+ and CD4+ TIL infiltration (p=0.003, p=0.008, and p=0.016, respectively). In contrast, low CXCR3 expression was correlated with greater tumor invasion depth, III/IV TNM stage, lymph node metastasis, and more poorly differentiated tumor cells in GC patients (p=0.001, p=0.005, p=0.037, and p=0.004, respectively). Univariate analysis indicated that patients with high CXCR3 expression and high DC and CD8+ TIL infiltration had longer OS (log-rank test, p<0.001, p=0.018, and p=0.001, respectively). Univariate and multivariate analyses indicated that CXCR3 expression was an independent prognostic factor for OS (p<0.001, in both cases). Conclusion: Thus, this study indicates that CXCR3 overexpression in GC is associated with increased DC and TIL infiltration and improved OS, and thus can be further exploited as a biomarker of favorable prognosis and a therapeutic target in GC.