GSE130679 Tumor endothelial up-regulation of IDO1 limits the response to CD40-stimulating immunotherapy

Contributors : M Georganaki ; M Ramachandran ; S Tuit ; N Nunez ; A Karampatzakis ; G Fotaki ; L van Hooren ; H Huang ; R Lugano ; T Ulas ; A Kaunisto ; E Holland ; P Ellmark ; S M Mangsbo ; J L Schultze ; M Essand ; S Tugues ; A DimbergSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusCD40-stimulating immunotherapy elicits potent anti-tumor responses, which are mainly T-cell dependent. Here, we have investigated how tumor endothelial cells respond to CD40-stimulating immunotherapy by isolating endothelial cells from B16.F10 melanoma in anti-CD40 treated or isotype treated mice followed by RNA-sequencing. Gene set enrichment analysis revealed an increase in interferon-  related responses in tumor endothelial cells following anti-CD40 therapy. The immunosuppressive enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) was preferentially expressed in endothelial cells, and it was up-regulated upon anti-CD40 treatment. IDO1 expression in tumor endothelium was positiv ely correlated to T-cell infiltration and to increased expression of IFNγ in the tumor microenvironment. In vitro, endothelial cells up-regulated IDO1 in response to T-cell-derived IFNγ, but not in response to CD40-stimulation. Combining agonistic anti-CD40 therapy with the IDO1 inhibitor epacados tat delayed tumor growth and increased survival in B16.F10 tumor-bearing mice, which was associated with increased activation of tumor-infiltrating T-cells. Hereby, we...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research