TMET-15. INVESTIGATING THE IL4I1-AHR AXIS IN GLIOBLASTOMA METABOLISM

Abstract Glioblastoma (GB) is the most frequent and malignant form of primary brain tumors in adults. Despite multi-modal therapy consisting of surgery, radio- and chemotherapy, tumors recur and overall survival remains poor. Previously, we identified that besides the classical tryptophan-catabolizing enzyme tryptophan-2,3-dioxygenase (TDO2), the L-amino acid oxidase interleukin-4-induced 1 (IL4I1) is able to activate the transcription factor aryl hydrocarbon receptor (AHR) via production of downstream metabolites. Activation of the AHR in GB may promote tumor progression e.g. by inhibiting anti-tumor immune responses. In this study, we aim to elucidate further the specific effects of the metabolic enzyme IL4I1 and its metabolites on AHR activation in GB. Further, we set out to identify and validate novel AHR target genes downstream of IL4I1. Harnessing the IL4I1-AHR axis might lead to the development of novel therapy strategies helping to overcome resistance in GB in the future.