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

Abstract

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.