Fig. 4
TCF7+ progenitor-like memory CD8+ T cells exhibit immunosuppressive characteristics in metastatic liver tumors. A–C Semi-supervised pseudotime trajectory of CD8+ T cell clusters inferred by Monocle2. Trajectory is colored by the pseudotime (A) or cell clusters (B). C Ridgeline plot showing the order of appearance of cell clusters in time colored by cell clusters (top), and the heatmap showing fluctuation of genes along the pseudotime (bottom). D Feature plots of the typical memory marker genes in each of CD8+ T cell clusters. The TCF7+ Tpm cells are circled by dashed lines. E Heatmap of pair-wise correlation coefficients (Spearman correlation analyses) showing the similarity of signature scores between TCF7+ Tpm and pre-defined CD8+ T cell clusters. F Dotplot showing the percentage of expressed cells and average expression levels of TdLN-TTSM marker genes, exhaustion, and effector-related genes among 4 CD8+ memory T cell clusters. TdLN-TTSM, tumor-draining lymph nodes (TdLN) tumor specific memory T cells (TTSM). G Scatter plot showing the correlation of signatures scores between TCF7+ Tpm and TdLN-TTSM in TCF7+ CD8+ T cells based on scRNA-Seq data. H Heatmap showing the average activities of the top 5 significant transcription factors (TFs) identified by SCENIC in each CD8+ T cell cluster. I Feature plots showing the activities of TCF7+ Tpm-specific transcription factor HOXB2 (top) and the expression levels of HOXB2 (bottom). J Volcano plot showing the differential expressed genes (DEGs) between TCF7+ Tpm and other memory CD8+ T cells. The red dots represent the statistically significant up-regulated genes, the blue ones represent the down-regulated genes, and the grey ones represent the non-significant genes. Of note, the green boxes mark the p38 MAPK cascade-associated genes and the orange boxes indicate the TGF-beta-SMAD-associated genes. K Barplot showing the GO biological processes enriched by the highly and lowly expressed genes in TCF7+ Tpm cells compared with other memory CD8+ T cells. The red and blue bars represent the GO biological processes enriched by the up-regulated genes and down-regulated genes, respectively. L Violin plots showing the GSVA scores of TCF7+ CD8+ Tpm cells signature genes across NTs and PTs from the TCGA-LIHC cohort (NTs, n = 50; PTs, n = 374) and MTs from the MT2020 cohort (n = 198). Wilcox test was used to assess the difference between groups. “****” and “ns” represent “P < 0.0001” and “not significant”, respectively. M Spatial distribution of the whole T/NK cells and TCF7+ Tpm cells in a metastatic liver tumor (L1) determined by the spatial transcriptomic data (GSE225857)