ME-19 * ANALYSIS OF TREG RECRUITMENT AND FOXP3 EXPRESSION IN GLIOMAS REGARDING THE INTRAOPERATIVE FLUORESCENCE OF 5-ALA

Abstract

Not only are regulatory T cells (Tregs) an essential component of the immune system in maintaining immunologic self-tolerance but they are also involved in the suppression of anti-tumor immune responses. The transcription factor forkhead box P3 (FOXP3) is widely used as a marker for the identification of Tregs being essential for the functionality. Oral 5 aminolevulinic acid (5-ALA) is used to assist surgical resection of high-grade gliomas, being known as an indicator of malignancy as it is able to pass the blood brain barrier in high-grade gliomas. Gaining more knowledge regarding the pathogenesis of gliomas, the tumor microenvironment came to the fore. In this study, patterns of Treg recruitment and FOXP3 expression in the microenvironment of gliomas were characterized, regarding the fluorescence of 5-ALA. Glioma tissue positive and negative for intraoperative fluorescence of 5-ALA was analyzed and compared. Tregs present in the tumor microenvironment were detected by double-immunohistochemistry for FOXP3 and the glioma marker, antiglial fibrillary acidic protein (GFAP). FOXP3 mRNA expression was examined, using quantitative real-time-PCR. Tregs were found in the tumor microenvironment as well as within tumor cell islets, and FOXP3 mRNA expression in the tumors was significantly higher than in normal brain. Intriguingly, single FOXP3+ cells exhibited morphologic characteristics of glioma cells. 5-ALA positive tumor tissue showed a higher accumulation of Tregs than 5-ALA negative tissue. Gliomas recruit Tregs into their microenvironment, presumably in order to suppress immunosurveillance, thus avoiding destruction by the immune system. Endogenous FOXP3 expression in glioma cells might present a novel mechanism of immune escape. Our study showed differences between the amount of Treg and FOPX3 expression in 5-ALA positive and negative glioma tissue indicating that Tregs are more present in high-grade malignant gliomas. These findings suggest FOXP3 and Tregs as a possible therapeutic target in the therapy of gliomas.