Tumour-infiltrating T-cell subpopulations in glioblastomas

Abstract

This study was designed to determine the incidence and prognostic value of various populations of tumour-infi ltrating T cells in glioblastomas. We also evaluated the diff erence 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 fi rst 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 Ϯ 1.8 CD31 T cells, 1.5 Ϯ 0.5 CD41 T cells, 6.8 Ϯ 1.3 CD81 T cells and 0.6 Ϯ 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 diff erence in the subpopulations between the fi rst 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 signifi cant diff erence in progression-free survival for CD8 (p ϭ 0.02) and overall survival for RTOG-RPA classes (p ϭ 0.003), the extent of removal (p ϭ 0.01) and MGMT promoter methylation status (p ϭ 0.005). Based on multivariate analysis, RTOG-RPA classes were signifi cantly 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 signifi cant diff erence in progression-free survival for CD81 T cells in immunologically privileged central nervous system.

Epigenetic biomarkers of T-cells in human glioma

“…With respect to tumor T-cell infiltrates in glioma tissue, our results are consistent with the published literature in several significant ways. Similar to previous reports, we found that T-cell and Treg infiltrates in tumor tissue increase with glioma grade, 10,43 that the fraction of Tregs/T-cells was increased in glioma tissues compared with blood implicating an active infiltration and accumulation in tumor tissue, and we found that CD8 cells represent about 60% of the T-cells in GBM tissues compared with 77% 44 or 40% 43 in previous studies. Hussain et al reported that CD8 cells were about 30% of identified T-cells but their study acknowledge significant problems with autofluorescence in their flow analysis making the identification of CD4 cells problematic.…”

Immunological challenges for peptide-based immunotherapy in glioblastoma

“…43 Although a remarkable amount of tumor-infiltrating lymphocytes (TIL) seems to be tumor-antigen specific, most of them do not execute any effector functions or contribute to tumor regression -they virtually have been rendered silent. [44][45][46] Especially, highgrade gliomas have been shown to suppress, modulate and evade the immune system at multiple levels. 27,41 Hereby the tumor not only alters its immunological appearance, but also plays an active role by manipulating the immune system in its favor.…”

Circulating T regulatory cells migration and phenotype in glioblastoma patients: an in vitro study

“…Although the role of various factors involved in the immune response on clinical evolution of glioma patients is suggested by a number of studies, the specific role of Treg in GBM progression requires further investigations [13,14,22]. In fact, while the study by Kim did not show a predictive value of FOXP3 expression in tumor specimens on progression and survival in a group of 67 GBM patients [22], the study from Fig.…”

“…In fact, while the study by Kim did not show a predictive value of FOXP3 expression in tumor specimens on progression and survival in a group of 67 GBM patients [22], the study from Fig. 2 a Mean migration ratios of Treg in patients (GBM) and healthy controls (CTR).…”