Fig. 2: MacroH2A-deficient melanomas deregulate genes associated with an immune anti-tumour response, and accumulate monocytes and dysfunctional CD8+ T cells.
a, GSEA of hallmark pathways performed on bulk RNA-seq of triallelic melanomas at 50 DPI. dKO versus WT comparison. The top ten significant (Benjamini–Hochberg adjusted P < 0.05) pathways are shown. Exact P values are provided in Supplementary Table 1. b, Heatmap of DEGs in WT and dKO melanomas (bulk tumour), grouped under selected top gene enrichment terms defined using Homer analysis. Each column represents an independent tumour. Expression values are normalized row-wise as Z-scores. c, Quantification of indicated non-overlapping tumour-infiltrating immune cell populations at 50 DPI, determined by flow cytometry. nWT = 12, ndKO = 15 except for the natural killer (NK) cell population, for which nWT = 8 and ndKO = 11. DC, dendritic cells; MHC, major histocompatibility complex. d, Proliferative status of CD8+ T cells in c assessed as a percentage of Ki-67 positivity by flow cytometry. e, Expression of PD-1 ligands on immune cells assessed as a percentage of PD-L1 or PD-L2 positivity by flow cytometry. For d and e, nWT = 8, ndKO = 9. For c–e, Mann–Whitney two-tailed test P values shown: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, with exact P values provided as numerical source data. The centre line represents the median. Non-significant differences are not labelled. f, GSEA of hallmark pathways performed on RNA-seq of CD8+ T cells sorted by flow cytometry from melanomas at 50 DPI. dKO cells versus WT comparison. g, Heatmap of DEGs in WT and dKO melanoma-infiltrating sorted CD8+ T cells, grouped under selected top gene enrichment terms defined using Homer analysis. Each column represents target cells from an independent tumour. Expression values are normalized row-wise as Z-scores.
