LABORATORY INVESTIGATION The prognostic value of Foxp3+ tumor-infiltrating lymphocytes in patients with glioblastoma

Abstract Forkhead box protein 3 (Foxp3) is known as a specific marker for regulatory T cells which contribute to immunosuppression in tumor microenvironment. However, existing studies regarding clinical significance of Foxp3? tumor-infiltrating lymphocytes (TILs) in glioblastoma (GBM) remained discrepant. In this study, we aimed to explore whether this subtype of TILs correlated with prog-nosis in patients with GBM. Foxp3? TILs as well as CD8? ones were detected by immunohistochemistry on paraffin-embedded tumor samples from 62 patients. Staining for p53, MGMT and Ki-67 were also performed. The correlation of TIL subtypes with clinicopathologic features were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method and compared using log-rank test. Independent prognostic factors for PFS and OS were determined through univariate and multivari-ate analysis. Significant correlation was found between Foxp3 and CD8 expression (P = 0.003), but not between TIL subtypes and clinicopathologic characteristics. Patients with higher density of Foxp3? TILs showed relatively shorter PFS (P \ 0.001) and OS (P = 0.003) whereas patients with higher density of CD8? TILs obtained no significant differences in survival. Survival analysis based on molecular classifications further clarified these predictive values. Univariate and multivariate analysis revealed that frequency of Foxp3? TILs was probably associated with both PFS (P = 0.002) and OS (P = 0.003). In conclusion, the results suggest that Foxp3 positive infiltrates could provide an independent predictive factor in GBM