Fig. 6: IFNα and IL-12 rewire immune circuits within the metastatic microenvironment enabling TA-specific T cell activity.

A Clonotype sharing between liver CD8⁺ T cells, grouped by TCR clonotype (n = 3 mouse/group). B UMAP projection of scRNA-seq of liver T and NK cell subclusters in left panel, in the right panel representation of shared and expanded CD8⁺ T cells. C GSEA of scRNA-seq data showing NES for selected GO terms calculated based on genes differentially expressed in putative tumor reactive CD8⁺ T cells in the indicated comparisons (n = 3 mice/group; statistical analysis by an adaptive multi-level split Monte-Carlo scheme; *: padj < 0.05; **: padj < 0.005; ***: padj < 0.0005). D Combined gene expression score for genes belonging to the indicated categories in the indicated tissue in putative tumor-reactive CD8⁺ T cells. E Top 50 differential ligand-receptor pairs obtained by MultiNichNet analysis of the tumor scRNA-seq, depicted in circos plots. On the top, TA33, on the bottom TA33.Combo. The arrow indicates the direction from sender to receiver cell type, and the color of the arrow indicates the sender cell type that expresses the ligand. F Heatmap showing the co-localization score of transcripts detected by MERSCOPE on liver tissue sections, collected from mice treated with TA33 or TA33.Combo LV, as described in Methods. Samples included both healthy liver parenchyma and liver metastases. The co-localization score was calculated by comparing transcript in TA33.Combo vs TA33 treated animals.