Imps-14prognostic role of regulatory t-cells in primary and recurrent meningioma

Although aggressive meningiomas WHO II and III are rare tumors, more effective therapies are urgently needed as reflected by a 5-year-recurrence rate of 50-80% in WHO III meningiomas. In the present study we aimed to learn more about the immunological situation of meningioma and thus a potential suitability of immunotherapeutic approaches. Occurrence of tumor-infiltrating lymphocytes (TILs) was studied in 114 primary and recurrent meningiomas WHO°I – III and quantified by multicolor immunofluorescence stainings using the markers CD3, CD8, and FOXP3 by using the semi-automated analysis method TissueFAXS. Although similar levels of TILs (CD3+) were found in all WHO grades, TIL numbers were higher in primary as compared to recurrent meningiomas. Phenotypic subclassification into effector and regulatory T-cells revealed elevated levels of T helper cells (CD8−) but not cytotoxic T-cells (CD8+). In contrast to effector T-cells, we found a significant increase of regulatory (FOXP3+) T-cells, which is mainly based on the CD8+ Treg cell phenotype. In contrast to all other T-cell phenotypes analyzed, solely FOXP3+ and in particular the CD8+ Treg cell subpopulation were increasing when comparing primary and recurrent meningioma and were further found to be correlated with a poor overall survival. Moreover, detection of Treg cells in primary meningioma is more frequently in patients developing recurrent tumors and might therefore serve as a negative prognostic marker. Furthermore, microarray analyses hint to profound changes in the tumor microenvironment with increasing WHO grade and recurrent tumors. Altogether, our results suggest a higher impact of quality than quantity of TILs, highlighting the importance of the microenvironment on the functional immune status, which needs to be considered for developing novel therapy approaches.