Introduction: Regulatory T-cells (Tregs) have been well characterized as a suppressive T-cell population, which play an important role in suppressing active immune responses and preventing potential immunopathologies. Specifically in various malignant cancer types, including GBM, a higher than normal population of regulatory T-cells has been well documented in both the tumor site as well as systemically, and have been implicated as potential mechanism of persistent local and systemic immune suppression. The purpose of this present study was to further understand the relationship between naïve T helper cells, B7-H1 (PD-L1), GBM and the increased presence of Treg cells.
Methods: Primary naïve T cells were co-cultured with primary GBM lines and fractions of T helper and Treg cells were analyzed. These effects were analyzed using flow cytometry in the absence and presence of siRNA transfected GBM lines. Co-culture was also performed with AKT inducible cell lines, to elucidate the pathway of this interaction.
Results: Flow cytometry analysis demonstrates a preponderance of T regulatory cells following co-culture of naïve T cells with primary glioma lines. This effect is reduced when B7-H1 expression is blocked with siRNA transfection against B7-H1 or with AKT pathway alterations.
Conclusions: Following co-culture with glioblastoma the Tregulatory cell population is increased as a result of direct interactions with B7-H1 and its ligand. This effect was reduced when B7-H1 interactions were blocked. This pathway is potentially mediated in part through an AKT dependent pathway.
Patient Care: This piece of basic science work is an attempt to understand the immunosuppressive pathophysiology of GBM. Further understanding of this mechanism could one day lead to new and improved therapies.
Learning Objectives: To understand the role of B7-H1 mediated immune suppression in glioblastoma.