Role of Th17/IL-17 inflammatory axis in the progression of malignant gliomas (P2095)

Recent studies on extra-cranial tumors have demonstrated a strong relationship between tumor progression and inflammation. The Th17 cells, an inflammatory T cell subtype, have been implicated with either pro- or anti-tumor activity, depending on the tumor type. Th17 cells or the cytokine IL-17 remain to be studied in malignant gliomas. The objective of our study is to explore the axis of inflammatory interactions in glioma progression by focusing on the functional significance of IL-17 and IL17 receptor (IL17R) in the tumor. Our experimental strategies include in vitro 3D culture of IL17R+ glioma cells for proliferation/differentiation and cell signaling assays and ex vivo analysis of clinical glioma tissues via multi-color flow cytometry and immunohistochemistry. We report here that: 1) There is considerable prevalence of IL-17-secreting and IL17-inducing (Th17 and CD11b+ myeloid) cells among glioma-infiltrating immune cells; 2) Th17 cells induced by glioma-derived factors, in the presence of TGF-β1, shows potential immune-suppressive phenotype; 3) IL17R is preferentially expressed in glioma stem-like cells (GSCs); 4) IL17 enhances the proliferation of GSCs in matrigel cultures; 5) IL17 induces phosphorylation of STAT3, NF-κB, and GSK-3β, while also enhancing β-catenin activity in GSCs. This study provides novel insight into inflammatory axis in glioma progression, which may have significant impact on clinical interventions in patients with malignant gliomas.