Fig. 7: MKC8866 + anti-PD-1 combination therapy reprograms the TME landscape and enhances CD8+ T and NK cell infiltration.

scRNA-seq was performed on tumor samples from the experiment presented in Fig. 6D and E (six tumor samples per group were pooled for scRNA-seq). A Different colors in the UMAP plot represent the assigned cell types identified based on the marker genes in Supplementary Fig. 7 A. B The table displays the percentage abundance of each cell type within the TME and the observed percentage changes for the different treatments compared to vehicle. C Volcano plot indicates the up- and down-regulated genes in the CD8+ T cell cluster in the scRNA-seq data from tumor samples of mice treated with MKC8866 + anti-PD-1 compared with vehicle. Notable up- and down-regulated genes were highlighted as red and blue, respectively. D The dot plot displays selected GSEA results (for hallmark gene sets) from scRNA-seq data for the different treatments compared to vehicle. Significantly up- or down-regulated pathways are depicted in red and blue, respectively. Dot size corresponds to the -log10 (p-value) of each pathway for the respective cell type. E Volcano plots indicate the up- and down-regulated genes in the indicated TAM subtypes for combination therapy vs vehicle. Notable up- and down-regulated genes are highlighted as red and blue, respectively. F) Chord plot displaying the result from CellChat analyzes showing the MHC-I signaling pathway interaction between indicated cell types from tumor samples of mice treated with combination therapy. G The Venn diagram summarizes the differentially expressed genes (p < 0.05) that were significantly altered in the CD8+ T cell cluster from tumors of combination therapy compared to the differentially expressed genes (p < 0.05) in the scRNA-seq data from the CD8+ T cell cluster in pembrolizumab + enzalutamide responsive versus non-responsive mCRPC patient samples as reported previously³⁵. H The heatmap indicates the log₂ fold-change expression of overlapping genes from Figure G in the CD8+ T cell cluster from tumors of mice for the indicated treatments compared to vehicle treatment. The Wilcoxon rank-sum test implemented in Seurat was used for Figures (C, E, and G).