The correlation between tumor-infiltrating Foxp3+regulatory T cells and cyclooxygenase-2 expression and their association with recurrence in resected head and neck cancers

The aim of this study was to investigate the correlation between tumor-infiltrating CD4+ CD25(high) Foxp3+ naturally occurring regulatory T cells (Foxp3+ nTregs) and cyclooxygenase-2 (COX-2) expression and their association with local recurrence in resected head and neck cancers. Intratumoral COX-2 and Foxp3+ nTregs expressions were retrospectively assessed using immunohistochemistry. Associations between the clinicopathological characteristics and either intratumoral COX-2 expression or number of Foxp3+ nTregs were tested using the Chi-square test. The correlation between the number of Foxp3+ nTregs and COX-2 expression was tested using Spearman's rank correlation test. Associations between recurrence-free survival (RFS) and either intratumoral COX-2 expression or number of Foxp3+ nTregs were calculated using the Kaplan-Meier method, and factors that may influence the RFS were analyzed by Cox regression. The five-year RFS for all patients was 35.09%. Patient clinicopathological characteristics had no relationship with intratumoral COX-2 expression or the number of Foxp3+ nTregs. However, a positive correlation between intratumoral COX-2 expression and the number of Foxp3+ nTregs was observed (P < 0.001). The RFS of patients with elevated COX-2 expression was significantly worse than that of patients without intratumoral COX-2 expression (P = 0.0228). The RFS of patients with tumors containing > 6 Foxp3+ cells was significantly worse than that of patients with tumors containing a parts per thousand currency sign6 Foxp3+ cells (P = 0.0020). However, by Cox regression analysis, the RFS of all patients was not influenced by intratumoral COX-2 expression (P = 0.100) or the number of Foxp3+ nTregs (P = 0.071). Tumor-infiltrating CD4+ CD25(high) Foxp3+ nTregs were positively correlated with intratumoral COX-2 expression and were associated with a worse RFS in univariate analysis.