Fig. 5: Systemic administration of AC484 in mice enhances IL-2–pSTAT5 signalling in the TME and induces a distinct T cell differentiation state.
From: The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity
a, UMAP of 20,035 re-clustered lymphoid cells that belonged to clusters identified in the original projection as expressing transcripts for Cd8a, Ncr1 or Cd4. b, Cell density projections by condition. c, PCA of ATAC–seq and RNA-seq samples. d, Unbiased K-means clustering of normalized peak intensity for differential OCRs (left). Average normalized mRNA expression of genes adjacent to peaks in each module (right). In both plots, values represent the average of two replicates. e, ATAC–seq tracks of the Tox and Il7r loci for TIM-3+ samples. Grey shaded regions are significantly differential between conditions. Two replicates shown per condition. f, Heatmap of RNA-seq-derived GSEA for memory, effector and exhausted CD8+ T cell gene sets (Methods) in all relevant pairwise comparisons. g, RNA-seq-derived GSEA of hallmark IFNγ, IFNα and inflammatory response, and IL-6–JAK–STAT3 and IL-2–STAT5 signalling gene sets significantly enriched in AC484 TIM-3+ compared with anti-PD-1 TIM-3+ samples. False discovery rate (FDR) for all was <0.1. h, Differential enrichment measured by hypergeometric test of hallmark gene sets in adjacent genes of differential OCRs between AC484 TIM-3+ and anti-PD-1 TIM-3+ conditions. i, TF motif enrichment analysis (Methods) of differential OCRs in AC484-treated TIM-3+ T cells relative to control (y axis) or anti-PD-1 (x axis) treated TIM-3+ samples. –log(FDR) values calculated using binomial tests are plotted on the axes. j, GSEA of IL-2 and anti-PD-L1 and of anti-PD-L1 gene sets (data are from ref. 37) between AC484 TIM-3+ and anti-PD-1 TIM-3+ RNA-seq. FDR for both was <0.001.
