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

J Neurooncol. 2014 Jan;116(2):251-9. doi: 10.1007/s11060-013-1314-0. Epub 2013 Nov 26.


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 prognosis 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 multivariate 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / radiotherapy
  • CD8 Antigens / metabolism
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Glioblastoma / diagnosis*
  • Glioblastoma / radiotherapy
  • Humans
  • Ki-67 Antigen / metabolism
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / metabolism
  • Young Adult


  • CD8 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Ki-67 Antigen
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes