Figure 2.
Oligoclonal T-cell expansion in a CAR T-cell–treated patient with acquired BM deficiency. (A) Expression of CD57 in CD8+ T cells in pretreatment and posttreatment samples and in an HD control. (B) Expression of the CAR construct in CD8+ T cells in pretreatment and posttreatment samples (left), and expression of CD57 in CD8+ CAR T cells (right). (C) t-SNE plot of single-cell gene expression in PBMCs of pretreatment and posttreatment samples. Cells formed graph-based clusters based on transcriptome similarity and cell types were assigned to cell clusters (left). Expression of well-established surface markers (CD3, CD4, CD8, CD19, CD11c, and CD56) in top 20% cells were highlighted on the same t-SNE plot (right). (D) A heat map plot showing the number of shared CDR3 sequences among top 200 TCR clones of pretreatment and posttreatment samples. On both x-axes and y-axes, samples of the patient and HD are depicted; paired samples (pretreatment and posttreatment) are adjacent. Numbers indicate counts of identical T-cell receptor (TCR) clones shared among samples. The color scheme (red to light blue) indicates the number of shared TCR CDR3 sequences from high to low. (E) Skyscraper plots showing for Vβ/Vα and matching Jβ/Jα in pretreatment and posttreatment samples. (F) Gini index of TCR clone size distribution was compared in pretreatment and posttreatment samples and with reported HDs and patients with T-LGLL.17 (G) Ranking of the top 10 TCR clonotypes from pretreatment and posttreatment samples. Blue lines indicate the top 5 clones before treatment; red lines indicate the top 5 clones after treatment. CDR3 sequences and clone sizes (cell count) of top 10 clones in pretreatment and posttreatment samples are depicted to the right of the graph, respectively. (H) GSEA plots of differentially expressed genes of the dominant clone vs all the other clones in posttreatment samples. (I) Bar plot showing top upregulated pathways in the dominant clone of the posttreatment sample as analyzed by Genomatix using top differentially expressed genes. t-SNE, t-distributed stochastic neighbor embedding.

Oligoclonal T-cell expansion in a CAR T-cell–treated patient with acquired BM deficiency. (A) Expression of CD57 in CD8+ T cells in pretreatment and posttreatment samples and in an HD control. (B) Expression of the CAR construct in CD8+ T cells in pretreatment and posttreatment samples (left), and expression of CD57 in CD8+ CAR T cells (right). (C) t-SNE plot of single-cell gene expression in PBMCs of pretreatment and posttreatment samples. Cells formed graph-based clusters based on transcriptome similarity and cell types were assigned to cell clusters (left). Expression of well-established surface markers (CD3, CD4, CD8, CD19, CD11c, and CD56) in top 20% cells were highlighted on the same t-SNE plot (right). (D) A heat map plot showing the number of shared CDR3 sequences among top 200 TCR clones of pretreatment and posttreatment samples. On both x-axes and y-axes, samples of the patient and HD are depicted; paired samples (pretreatment and posttreatment) are adjacent. Numbers indicate counts of identical T-cell receptor (TCR) clones shared among samples. The color scheme (red to light blue) indicates the number of shared TCR CDR3 sequences from high to low. (E) Skyscraper plots showing for Vβ/Vα and matching Jβ/Jα in pretreatment and posttreatment samples. (F) Gini index of TCR clone size distribution was compared in pretreatment and posttreatment samples and with reported HDs and patients with T-LGLL.17 (G) Ranking of the top 10 TCR clonotypes from pretreatment and posttreatment samples. Blue lines indicate the top 5 clones before treatment; red lines indicate the top 5 clones after treatment. CDR3 sequences and clone sizes (cell count) of top 10 clones in pretreatment and posttreatment samples are depicted to the right of the graph, respectively. (H) GSEA plots of differentially expressed genes of the dominant clone vs all the other clones in posttreatment samples. (I) Bar plot showing top upregulated pathways in the dominant clone of the posttreatment sample as analyzed by Genomatix using top differentially expressed genes. t-SNE, t-distributed stochastic neighbor embedding.

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