Extended Data Fig. 9: Helios-expressing CD57⁺T-bet⁺ CAR T cells display an NK-like transition program.

a, Pearson correlation between percentage of CD57^–Helios⁺ cells among CD4⁺ CAR T cells and expansion of CAR T cells, quantified as log10 AUC_0-28 for all study patients with available data (n = 49). P value is from the correlation test. b, Percentage of CD57^–Helios⁺ cells among CD4⁺ CAR T cells separated by maximum ICANS grade and day of maximum ICANS (n = 54). c, Percentage of CD57⁺T-bet⁺ cells among CD4⁺ CAR T cells (left, n = 23) or CD8⁺ CAR T cells (right, n = 27) in blood on day 7 post-infusion separated by response at 6 months in patients from the validation cohort with ≥100 CD4⁺ or CD8⁺ CAR T cells detected, respectively. d, Scatter plot showing percentage of CD57^–Helios⁺ vs. CD57⁺T-bet⁺ cells among CD4⁺ CAR T cells in both discovery and validation cohorts (n = 54). e, Percentage of Helios⁺ cells among CD4⁺CD57⁺T-bet⁺ cells separated by response at 6 months in patients from the discovery (left, n = 21) or validation (right, n = 19) cohorts with ≥10 CD4⁺CD57⁺T-bet⁺ CAR T cells detected. f, Volcano plot showing differentially expressed genes comparing Helios⁺ to Helios^– cells within CD57⁺T-bet⁺ CAR T cells (n = 774 cells) using scRNA-seq data from 9 LBCL patients on day 7 following axi-cel infusion. Differentially upregulated genes are in red; genes used to define each population are in black. g,h, Violin plots showing selected T cell (b) or NK-related (h) gene and surface protein expression in Helios^– and Helios⁺ cells within CD57⁺T-bet⁺ CAR T cells (n = 774 cells). Stars denote significant (P < 0.05) upregulation in the indicated population relative to the population without a star. Boxplots in (b,c,e) show quartiles with a band at median, whiskers indicating 1.5x IQR, and all observations overlaid as dots. P values were calculated using two-sided Wilcoxon-Mann Whitney U test.