Extended Data Fig. 7: AC484 induces transcriptional and epigenetic programs that promote effector function and reduce T cell exhaustion.
From: The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity
a, Schematic representing experimental design for ATAC-seq and RNAseq sequencing of tumour-infiltrating lymphocytes from B16 tumours from untreated (n = 14), anti-PD-1- (n = 14) or AC484-treated (n = 19) mice; figure created with BioRender.com. b, Number of called peaks for each sample condition (Methods). c, Number of differential open chromatin regions between conditions (FDR < 0.05). Top row shows the comparison of AC484 SLAMF6+ vs anti-PD-1 SLAMF6+. Bottom row shows the comparison of NTX SLAMF6+ vs NTX TIM-3+. Color denotes the condition in which regions are differentially open. d, ATAC-seq tracks of the Gzma, Sell, and Tcf7 loci for TIM-3+ samples. Gray shaded regions are significantly differential between conditions. Two replicates shown per condition. e, Average normalized mRNA expression for genes called out in Fig. 5d. Colors are scaled per each column individually. f, Differential enrichment calculated by hypergeometric test of IL-2+anti-PD-L1 and anti-PD-L1 genesets in adjacent genes of differential OCRs between AC484 TIM-3+ and anti-PD-1 TIM-3+. Red denotes enrichment in AC484 TIM-3+. Blue denotes enrichment in anti-PD-1 TIM-3+.
