Bystander IFN- γ activity promotes widespread and sustained cytokine signaling altering the tumor microenvironment

The cytokine IFN-g produced by tumor-reactive T cells is a key effector molecule with well characterized pleiotropic effects during anti-tumor immune responses. While IFN-g production is a transient event targeted at the immunological synapse, how IFN-g acts in time and space within the tumor microenvironment has remained elusive. Specifically, the link between duration of exposure to the cytokine and cellular response is poorly understood. Using RNA sequencing, we show that tumor cell phenotypic alterations require several hours of exposure to IFN-g, most likely due to a positive feedback loop mediated by STAT1 and IRF8. Eµ-myc mouse cell line were stimulated by IFNg for various amount of time and harvested at 24 hours post stimulation. polyA mRNAs were then purified and RNAseq was performed