Fig. 6: Transcriptomic signatures of exhausted-like EM CD8+ CAR T cells.
From: Two-stage CD8+ CAR T-cell differentiation in patients with large B-cell lymphoma
UMAP depicting single-cell transcriptomes of peripheral blood CD8+ T cells colored by cell cluster (a) or density contours of each cluster (b). The exhausted-like EM cluster is located on the lower half of the UMAP. c Density maps depicting expression levels of major T-cell genes and proteins, divided into categories. In the “receptor” category, proteins are placed directly beneath the corresponding gene. d Flow plots for validating transcriptomic data. Plots depict expression of CD39 and CD57 (top row) or CX3CR1 (bottom row) in CD8+ CAR T cells at each timepoint from P2. Exhausted-like EM CAR T cells were expected to be Texp-specific with high CD39 and low CD57/CX3CR1 expression. e, f Heat map depicting normalized expression of major gene sets from Wherry et al. (e). Expression of two of the gene sets were depicted as violin plots (f), ordered by decreasing expression level per cluster (EM, exh-like: n = 7163 cells; CM: n = 1883 cells, EM: n = 4937 cells; TE, exh-like: n = 552 cells; TE: n = 21019 cells). The central line indicates the median. The bounds of the box indicate the 25th–75th percentile. The length of the whiskers indicates 1.5 times the inter-quartile range from the first and third quartiles. Expression levels were compared to that of the cluster with highest expression via two-sided Wilcoxon Rank-Sum test, with p values adjusted for multiple hypotheses testing using the Benjamini-Hochberg method, whereby **** indicates p < 0.0001, *** indicates p < 0.001. g Volcano plot depicting differentially expressed genes found via two-sided Wilcoxon Rank-Sum test with Bonferroni adjustment between EM and exhausted-like EM CD8+ CAR T cells. Genes were colored according to direction of upregulation. h Enrichment plots for select gene sets differentially expressed between EM and exhausted-like EM CD8+ CAR T cells. Enrichment scores are computed by the Kolmogorov-Smirnov test with false discovery rate (FDR) adjusted q-values. Source data are provided as a Source Data file.
