Avadomide induces IFN type I and II signaling in patient T cells encompassing activation, exhaustion, and cytotoxicity and normalizes deregulated IFN and chemokine gene expression in previously exhausted T cells. (A) Top differential hallmark pathways between vehicle and avadomide treatment. Normalized enrichment scores (NES) represent the mean score over avadomide-treated samples, with positive scores indicating upregulation with avadomide treatment relative to vehicle control. (B) Heatmap of top immune pathways enriched by avadomide treatment, shown under multiple treatment conditions. Cell colors indicate mean NES for each pathway, indicating directionality and strength of the gene pathway changes. (C) Heatmap of selected IFN genes deregulated by avadomide treatment shown under multiple treatment conditions for multiple patient subsets indicated. Cell colors indicate the mean log fold change of expression compared with vehicle control, with positive values (red) or negative values (blue) indicating upregulation or downregulation respectively compared with vehicle. (D) Barcode enrichment plot for a gene signature upregulated in age-matched healthy donor CD4⁺ T cells compared with CLL patient CD4⁺ T cells (GSE8835_HEALTHY_VS_CLL_CD4_TCELL_UP) that is significantly upregulated by avadomide treatment. These data support normalization of deregulated IFN gene expression in previously exhausted patient T cells toward a healthy T-cell transcriptome profile.