Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas

Purpose: The incidence of regulatory T cells (Treg) in intrinsic central nervous system malignancies is unknown. Immunotherapeutic approaches that inhibit the Treg population may be limited to a subset of patients with gliomas. Our hypothesis is that only the most malignant gliomas have a prominent glioma-infiltrating Treg population that contributes to the immunosuppressive biology and that the presence of Tregs is a negative prognostic variable. Experimental Design: We measured the incidence of Tregs in 135 glial tumors (including all pathologic types) in a glioma microarray using immunohistochemical analysis. Results were categorized according to the total number of Tregs within the tumors. Correlation of the presence of Tregs with prognosis was evaluated using univariate and multivariate analyses. Results: Tregs were not present in normal brain tissue and were very rarely found in low-grade gliomas and oligodendrogliomas. We observed significant differences in the prevalence of Tregs between astrocytic and oligodendroglial tumors, between tumors of different grades, and between different pathologic types of tumors. We identified Tregs most frequently in glioblastoma multiforme (GBM) but very rarely in low-grade astrocytomas. The presence of Tregs within GBMs did not alter the median survival in patients from whom the tumors were obtained. Conclusions: Treg infiltration differed significantly in the tumors according to lineage, pathology, and grade. Tregs seemed to have the highest predilection for tumors of the astrocytic lineage and specifically in the high-grade gliomas, such as GBM. In both univariate and multivariate analysis, the presence of Tregs in GBMs seemed to be prognostically neutral.