Extended Data Fig. 4: scRNAseq analyses reveal distinct alterations in the tumor immune microenvironment of mtDNA mutant tumors. | Nature Cancer

Extended Data Fig. 4: scRNAseq analyses reveal distinct alterations in the tumor immune microenvironment of mtDNA mutant tumors.

From: Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma

Extended Data Fig. 4

UMAP indicating a Ptprc expression, b epithelial score and c aneuploidy as determined by copykat prediction. These criteria were employed as the B78 cells lack distinct transcriptional signatures to allow unambiguous identification of malignant cells. d UMAP of seurat clustered T-cell/ NK cell scRNAseq from indicated samples. e UMAP indicating cell type IDs. NK, natural killer cells. IFN, interferon. Tgd, gamma delta T-cells. Treg, regulatory T-cells. f UMAP of seurat clustered myeloid scRNAseq from indicated samples. g UMAP indicating cell type IDs. cDC, conventional dendritic cells. Malignant cells were identified for scRNAseq analysis as aneuploid cells with low or nil Ptprc (CD45) expression and high epithelial score. GSEA of non-malignant cells with significant changes for h Ifna response, i Ifng response, j IL2-STAT5 signaling, k inflammatory response and l oxidative phosphorylation. m Heatmap of tumor resident myeloid cells with significant changes (p < 0.1) in proportion relative to the total malignant and non-malignant cells (n = 7, 3, 3, and 3 individual tumours). n Heatmap of tumor resident lymphoid cells with significant changes (p < 0.1) in proportion relative to the total malignant and non-malignant cells (n = 7, 3, 3, and 3 individual tumours). o Relative PD-L1 expression within each cell cells (n = 7, 3, 3, and 3 individual tumours). 60% mutant tumors are coloured the same, presented as m.12,436G>A and m.11,944G>A from left to right. p Harvested tumor weight at day 21 (n = 15, 10, 7, 10, 9 and 5 individual tumours). Two-tailed Wilcoxon signed rank test (H-l), two-tailed student’s t-test (M,N) or one-way ANOVA test with Sidak multiple comparisons test (P) were applied. Error bars indicate SEM (O) or SD (P). Measure of centrality is mean. * P = < 0.05, ** P = <0.01. Number of replicates are described across conditions from left to right as presented. Heatmap representations of data where asterisks are not present report non-significant changes NES: normalised expression score.

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