Inducible costimulator (ICOS) regulates the immune response in a mouse brain tumor model (127.12)

Abstract

Abstract Glioblastoma multiforme (GBM) is the most invasive form of brain tumors and average survival less than 14.6 months. Tumors in the central nervous system (CNS) are thought to be poorly immunogenic due to compartmentalization and immune specialization. However, presence of CD4+IL-17+ (Th17) and CD4+Foxp3+ regulatory T cells (Tregs) in GBM indicates that immune responses occur within the context of CNS-resident tumors. Inducible costimulator (ICOS) belongs to the CD28 family of costimulatory molecules. ICOS is upregulated on the surface of activated T cells and its interaction with ICOS ligand can shape diverse immune responses, such as differentiation of helper T cells and IL-10-secreting Tregs. Here, we hypothesized that ICOS plays a role in regulating T cell responses involved in tumor progression. To study the role of ICOS in tumor progression, wild-type (WT) and ICOS-deficient (ICOS-/-) mice were intracranially-implanted with murine GL261 glioma cells. The median survival of tumor-bearing ICOS-/- mice was reduced to 25 days from 30 days in WT mice. The data shows a two-fold reduction in frequency of intracranial Tregs in tumor-bearing ICOS-/- mice (p<0.01). Additionally, the frequency of intracranial CD4+IFN-g+ T cells increased 3-fold (p<0.02), accompanied by a trend for increased in Th17 cells in tumor-bearing ICOS-/- mice. Collectively this indicates a role for ICOS in regulation of brain tumor-specific immune response and provides rationale for further investigation.