Skip to main content
. 2026 Jan 3;17:753. doi: 10.1038/s41467-025-67446-5

Fig. 5. The chimeric CD8/CD28 co-receptor TCR-T cells have a reduced exhaustion(-like) phenotype in vivo.

Fig. 5

A Heatmap showing the top 20 differentially expressed genes identified within each cluster. The “top 20” refers to the 20 genes with the most significant differential expression across the identified clusters. The dendrogram on the left displays the similarity between the clusters, based on unsupervised clustering of gene co-expression patterns. The top dendrogram shows the relationships between the genes based on their expression patterns. B UMAP plot displaying the two-dimensional distribution of annotated T cell transcriptional states, colored by subset. Subsets were annotated according to gene co-expression patterns in (A). C UMAP plot of T cells colored by density and split by group (from left to right: CD8-alone TTCR-MA1-CD8αβ group, CD8 in TTCR-MA1-CD8αβ and CD8 in TTCR-MA1-CD8/CD28 from the combination group). The plot shows the two-dimensional distribution of T cells, with color intensity representing cell density, where dark red indicates higher density. D Violin plots displaying the expression levels (y-axis) of stem-like (TCF7, SELL, IL7R, LTB, LEF1, NELL2), proliferation (MKI67, TOP2A, PCNA), and cytotoxicity (KLRG1, KLRD1, NKG7, GZMB, GNLY, PRF1, GZMA, GZMM, CSTA, CSTW) markers across CD8 T-cell transcriptional states between CD8-alone and CD8 in TTCR-MA1-CD8αβ combo (x-axis). Statistical significance was assessed using a two-sided Wilcoxon rank sum test. Boxplots within violins show the median, interquartile range (box; 25th–75th percentiles), and whiskers extending to 1.5× IQR. E Tumor burden measurements for NSG mice engrafted with 1 × 105 cells A375F and subsequently infused with a total of 5 × 106 T cells of CD8-only TTCR-MA1-CD8αβ or CD4 and CD8 (1:1 ratio combo) TTCR-MA1-CD8αβ 12 days post engraftment. (n = 3 mice, 2 tumors/group averaged). p value determined by unpaired two-tailed t-test. Graph represents mean ± SEM. F Violin plots displaying the expression levels (y-axis) of stem-like (TCF7, SELL, IL7R, LTB, LEF1, NELL2), proliferation (MKI67, TOP2A, PCNA), and cytotoxicity (KLRG1, KLRD1, NKG7, GZMB, GNLY, PRF1, GZMA, GZMM, CSTA, CSTW) markers across CD8 T-cell transcriptional states between TTCR-MA1-CD8αβ and TTCR-MA1-CD8/28 (x-axis). Statistical significance was assessed using a two-sided Wilcoxon rank sum test. Boxplots within violins show the median, interquartile range (box; 25th–75th percentiles), and whiskers extending to 1.5× IQR. G Tumor burden measurements for NSG mice engrafted with 1 × 105 cells A375F and subsequently infused with total 5 × 106 T cells of CD4 and CD8 (1:1 ratio combo) TTCR-MA1-CD8αβ, and CD4 and CD8 (1:1 ratio combo) TTCR-MA1-CD8/28 12 days post engraftment. (n = 3 mice, 2 tumors/group averaged). p value determined by unpaired two-tailed t-test. The graph represents mean ± SEM.