Fig. 3. scRNA-seq of pre-infusion CAR-T products reveals cell-intrinsic defects associated with non-durable response.

UMAP projections of three datasets representing Kymriah in ALL (a–c), Kymriah in LBCL (d–f) and Yescarta in LBCL (g–i). a,d,g, UMAP projections annotated by response category. b,e,h, UMAP projections annotated as exhausted using ProjectTILs³³. c,f,i, UMAP projections annotated for high (above mean) or low (below mean) CAR-T cell dysfunction signature from Good et al.³⁵. j, GSEA for select pathways, comparing both exhausted versus non-exhausted and CR versus PR/RL/NR categories within cells annotated as T effector memory (Tem via ProjecTILs) or early memory (Tmem; CD8⁺CD45RO⁻CD27⁺ via CITE-seq). A positive normalized enrichment score (NES, blue) indicates higher enrichment in CR/non-exhausted cells. *NR = NR/RL or NR/PR. P values were calculated by Kolmogorov–Smirnov tests implemented in GSEA.