Tumour-infiltrating CD4(+) and CD8(+) lymphocytes as predictors of clinical outcome in glioma

Br J Cancer. 2014 May 13;110(10):2560-8. doi: 10.1038/bjc.2014.162. Epub 2014 Apr 1.


Background: T lymphocyte infiltration has been detected in glioma, although its significance remains unclear. The purpose of the present study was to explore the prognostic value of CD4(+) and CD8(+) tumour-infiltrating lymphocytes (TILs) in glioma, and the prognostic value of infiltrating Forkhead box protein 3 (FoxP3(+)) regulatory T cells were also investigated.

Methods: CD4(+), FoxP3(+) and CD8(+) TILs were assessed by immunohistochemical staining of tissue microarray cores from 284 gliomas. Kaplan-Meier analysis and Cox proportional hazards models were used to examine the survival function of these TILs in 90 glioblastoma patients.

Results: The number of CD8(+) TILs was inversely correlated with tumour grade (P=0.025), whereas the number of CD4(+) TILs was positively correlated with tumour grade (P=0.002). FoxP3(+) TILs were only observed in glioblastomas, but not in low-grade astrocytomas or oligodendroglial tumours. Among patients with glioblastoma, none of CD4(+) TILs, FoxP3(+) TILs and CD8(+) TILs alone was significantly associated with patient prognosis. However, the presence of high CD4(+) and low CD8(+) TIL levels was an independent predictor of poor progress-free survival (multivariate hazard ratio (HR) 1.618, 95% confidence interval (CI) 1.245-2.101, P<0.001) and poor overall survival (multivariate HR 1.508, 95% CI 1.162-1.956, P=0.002). Moreover, pseudoprogression was more often found in patients with high CD4(+) TILs and high CD8(+) TILs.

Conclusions: The combination of CD4(+) and CD8(+) TILs is a predictor of clinical outcome in glioblastoma patients, and a high level of CD4(+) TILs combined with low CD8(+) TILs was associated with unfavourable prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / pathology*
  • Central Nervous System Neoplasms / immunology
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / pathology*
  • Central Nervous System Neoplasms / therapy
  • DNA Methylation
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Forkhead Transcription Factors / analysis
  • Glioma / immunology
  • Glioma / mortality
  • Glioma / pathology*
  • Glioma / therapy
  • Humans
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • T-Lymphocytes, Regulatory / pathology
  • Tumor Escape


  • FOXP3 protein, human
  • Forkhead Transcription Factors