Extended Data Fig. 2: GD2-28z CAR T cells display an exhaustion signature at the single cell-level.
From: c-Jun overexpression in CAR T cells induces exhaustion resistance
a, Venn diagram showing overlapping genes in differential expression analysis of single cell data (red) and the top 200 genes driving the separation of CD19 and HA-28z CAR T cells in bulk RNA-seq (yellow, Fig. 1f). In total, 79 out of the top 200 genes from bulk RNA-seq are differentially expressed by DESeq2 analysis in GD2-28z versus CD19-28z single cells. Highlighted genes from the intersection include inhibitory receptors (CTLA4, LAG3, GITR), effector molecules (CD25, IFNG, GZMB), cytokines (IL13 and IL1A) and bZIP/IRF family transcription factors (BATF3 and IRF4). b, Heat map clustering the top 50 differentially expressed genes in GD2-28z versus CD19-28z single-cell transcriptome analysis. Each row represents one cell. c, Violin plots depicting individual gene expression in CD8+ GD2-28z and CD19-28z single CAR T cells. Genes upregulated in GD2 CAR T cells include inhibitory receptors, effector molecules and AP-1 family transcription factors, whereas CD19 CAR T cells have increased expression of memory-associated genes. P values determined by unpaired two-tailed Wilcoxon–Mann–Whitney U test.
