Fig. 3: Integration of clonotypic and phenotypic shifts supports a two-stage differentiation model.
From: Two-stage CD8+ CAR T-cell differentiation in patients with large B-cell lymphoma
All figure panels are based on the clonotype-phenotype linked dataset (n = 32432 cells). a Proportion of CAR T cells with an exhausted-like effector memory (EM-exh), terminal effector (TE), or other phenotypes at each timepoint. b Total abundance of all clones that were predominantly EM-exh at Texp (left), TE at Tper1 (middle), or TE at Tper2 (right), measured across timepoints. A clone’s predominant phenotype was defined as the phenotype with the greatest representation. Each point represents clones from a patient (n = 6). Abundance across timepoints were compared by repeated measures ANOVA with paired two-sided post hoc t tests, whereby **** indicates p < 0.0001, *** indicates p < 0.001, ** indicates p < 0.01, * indicates p < 0.05, and ns indicates not significant. c Overlay of clonal abundance dynamics with 95% confidence intervals for clones annotated as EM-exh from Texp (red) or TE from Tper1/Tper2 (blue). d Pie chart depicting proportion of the top 500 clones classified as Wave 1, Wave 2, or Other. e Heatmap depicting normalized CAR abundance across timepoints for the top 500 largest clones. f Clonal dynamics and phenotypic distribution for the top 500 clones, grouped into Wave 1 and Wave 2. Left panels depict the change in clonal abundance across timepoints, while right panels show the predominant phenotype distribution at each timepoint. g Cartoon summarizing the two-stage model for CAR T-cell differentiation. Bulk CAR T-cell expansion and contraction (black line) masks the dynamics of Wave 1 (EM-exh, expansion phase timeframe, red) and Wave 2 (TE, persistence phase timeframe, blue) clones. Created in BioRender. Hu, Y. (2025) https://BioRender.com/rwp4v6g. Source data are provided as a Source Data file.
