Fig. 7: Comparison of histone marks from CM-derived CAR-T from healthy donors and CM-enriched CAR-T from patients reveals exhaustion-associated transcription factors not seen by transcriptomic approaches.

A PCA plots of RNA-seq, H3K27me3 or H3K4me2 marks of CAR-T manufactured from healthy donor (HD) central memory (CM)-derived and patient (PT) CM-derived CD8 + T cells. B Numbers of differentially expressed (DEx by RNA-seq) or enriched (DEn by H3K4me2 or H3K27me3) genes when HD CM-derived CAR-T are compared to patient CM-derived CAR-T. C Volcano plot of -log(adjusted P value by Benjamini-Hochberg procedure) in transcript (left panel) or H3K4me2 (middle panel) or H3K27me3 (right panel) signal vs log(fold-change, FC). DEx/DEn genes are denoted purple for HD CM-derived CAR-T, or peach for patient CM-enriched CAR-T. Named genes are transcription factors (TFs) that are DEx/DEn in each analysis. D, E Mean scaled RNA transcript (D), H3K4me2 (E) and H3K27me3 (F) +/- SD signal +1 of exhaustion resistance-associated TF genes differentially expressed or enriched in patient and HD CM-derived CAR-T. Shown is adjusted P value by Benjamini-Hochberg procedure.