Fig. 5: AML induces TTCR-C4 NKL/Temra differentiation skewing. | Nature Communications

Fig. 5: AML induces TTCR-C4 NKL/Temra differentiation skewing.

From: A phase I/II trial of WT1-specific TCR gene therapy for patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation: skewing towards NK-like phenotype impairs T cell function and persistence

Fig. 5

A UMAP plot of CD8+ T cells colored by density and split by group (AML(-) and AML( + )). AML(+) samples are those with detectable leukemic cells in BM or PB, while AML(-) lack detectable disease. Color intensity reflects CD8+ T-cell density (blue = low, yellow = high). Dashed lines highlight areas of highest density in each group. B Point-range plot showing the pairwise (AML(+) vs. AML(-)) proportional difference for each CD8+ T-cell subset. Horizontal lines extending from each point denote the 95% confidence intervals of the log2FD. Colors indicate the statistical significance (red: FDR < 0.05, blue: FDR ≥ 0.05); vertical dashed lines mark the absolute value of log2FD cutoff for significance. C Heatmap displaying DGE of NKL genes across the CD8+ T-cell subsets in AML(-) vs. AML(+) (blue = low, red = high expression). Dashed boxes highlight NKL/Temra genes. D Line plots showing the absolute cell counts over time (days of coculture) for TTCR37-45 (dashed lines) and K562 cells (solid lines) at E:T ratios of 1:1 (sky blue) and 1:4 (tan). E Line plots showing the T-cell-to-tumor-cell ratio over time for each E:T condition (left: 1:4; right: 1:1). Cell ratios were calculated based on flow cytometry data. F Heatmap depicting significant DEGs across TTCR37-45_D0 (TTCR37-45-only), K562_D13 (TTCR37-45 T cells after 13 days of coculture with K562 AML cell line), K562_D23 (TTCR37-45 T cells after 23 days of coculture with K562 AML cell line) conditions. Signifcance was determined using DESeq2 (FDR < 0.05). Blue = low, red = high expression. G Boxplots illustrating the z-score of Exhaustion, NK-like, NaĂ¯ve-like and Tem signatures aross co-culture timepoints. Each box represents the distribution of z-scores for the genes in the respective signature at each timepoint. The center line indicates the median; the box limits represents the IQR, and the whiskers span 1.5 x IQR. H Heatmap illustrating the enrichment of the top 50 DEGs from scRNAseq-derived subsets (TTCR-C4, Tem, NaĂ¯ve-/cm-like, NKL/Temra, ISG, Tmem/prolif) and manually curated exhaustion markers across three comparisons: K562_D13 vs. TTCR37-45_D0, K562_D23 vs. TTCR37-45_D0, K562_D23 vs. K562_D13. Red = high, blue = low enrichment. TTCR37-45 represents the baseline (TTCR37-45-only condition).

Back to article page