Tumour-infiltrating T-cell subpopulations in glioblastomas.

Abstract

This study was designed to determine the incidence and prognostic value of various populations of tumour-infiltrating T cells in glioblastomas. We also evaluated the difference in T-cell populations after conventional treatment. Sixty-seven patients with glioblastomas underwent surgery between 2003 and April 2009. Immunohistochemical staining was performed for CD3, CD4, CD8 and FoxP3, and the average number and percentage of positive cells were calculated. In eight patients, the average number of subpopulations was compared between the specimens obtained during the first and second operations. Age, gender, Karnofsky performance status, Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) classes, extent of removal, treatment modality, O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and immunopositivity for CD4, CD8 and FoxP3 were analyzed as prognostic factors. There was an average of 12.8 ± 1.8 CD31 T cells, 1.5 ± 0.5 CD41 T cells, 6.8 ± 1.3 CD81 T cells and 0.6 ± 0.2 FoxP3 cells. The percentage of positive T-cell subpopulations was 89.6%, 22.4%, 77.6% and 34.3% for CD3, CD4, CD8 and FoxP3, respectively. In eight patients, there was no difference in the subpopulations between the first and second operations. The median progression-free survival was 7.0 months (95% CI, 5.2-8.9 months) and the overall survival was 14.8 months (95% CI, 11-18.7 months). Univariate analysis showed a statistically significant difference in progression-free survival for CD8 (p = 0.02) and overall survival for RTOG-RPA classes (p = 0.003), the extent of removal (p = 0.01) and MGMT promoter methylation status (p = 0.005). Based on multivariate analysis, RTOG-RPA classes were significantly associated with longer overall survival. The intratumoural immune response occurred frequently in glioblastomas and there was a consistent response, even after conventional treatment. There was a statistically significant difference in progression-free survival for CD81 T cells in immunologically privileged central nervous system.