Extended Data Fig. 1: CREM is upregulated in CAR-NK cells following adoptive transfer.
From: CREM is a regulatory checkpoint of CAR and IL-15 signalling in NK cells
(a) Heatmap of differentially expressed genes (DEGs; adjusted P value < 0.01 and absolute log2 fold change (FC) > 0.5) in CAR19/IL-15 NK cells post-infusion (day 7 and day 14) vs. pre-infusion from scRNA-seq data (Li et al. dataset14) based on Raji mouse model presented in Fig. 1; (b) UMAP expression plot of CREM; (c) CREM expression in the pre-infusion CAR-NK cell product and in CAR-NK cells isolated from mice over time; (d) Expression of select genes encoding calcium binding proteins that were identified to be overexpressed in post-infusion NK cells relative to pre-infusion NK cells; (e) UMAP distribution of cell cycle stages in CAR19/IL-15 NK cells; (f) Quantification of CREM expression pre- and post-infusion by stages of the cell cycle; (g) UMAP expression plot of IL-15 activity inferred by CytoSig (refer to Methods); (h) Quantification of IL-15 activity pre- and post-infusion; (i) Quantification of IL-15 activity pre- and post-infusion by stages of the cell cycle; (j) Scatter plot depicting the correlation between CREM and IL-15 activity pre- and post-infusion. Statistical comparisons were performed using one-way ANOVA followed by Tukey’s test for pairwise comparisons (c), one-way ANOVA (f,i), Wilcox Rank Sum test (d,h), and Spearman correlation (j).
