Interaction between tumor and myeloid cells induce/expand Th17 cells in malignant gliomas (48.28)

Abstract

Abstract Th17 cells, a recently discovered inflammatory T cell subtype, have been reported in several tumors, where they are implicated with either pro- or anti-tumor activity, depending on the tumor type. Th17 cells have not been studied with respect to brain tumors. We have been studying the mechanism of induction and role of Th17 cells in malignant gliomas using primary tumor as well as glioma cell lines. We report here that: 1) There is considerable prevalence of Th17 cells and myeloid (CD11b) cells among glioma-infiltrating immune cells; 2) Glioma cells express the cytokines TGF-β1 and IL-6, while the infiltrating myeloid cells express IL-1β and IL-23; 3) Naïve T cells cultured with anti-CD2/CD3/CD28-loaded microbeads in the presence of glioma culture supernatants differentiate into Th17 cells, which is inhibited by antibodies to TGF-β1 and IL-6; 4) Supernatant from glioma-monocyte co-culture generates significantly higher frequency of Th17 cells compared to glioma supernatant, which is abrogated by antibodies to IL-1β and IL-23. Moreover, 5) Th17 cells generated in the presence of supernatant from glioma-monocyte co-culture have low IFN-γ and high IL-10 expression, suggesting that glioma-associated Th17 cells may be immune suppressive. Further studies on the mechanism of tumor-infiltration, developmental pathways and pro-/anti-tumor functions of Th17 cells will provide rationale for developing novel adjuvant immunotherapeutic strategies for malignant gliomas.