Fig. 9: YUMM2.1 tumours spontaneously relapsing after α-PD-1 treatment are highly inflamed with T cells.

A RT-qPCR analysis of Cxcl10, Ifng, Stat1, Irf1, and Parp14 mRNA expression levels in YUMM2.1 tumours which (relapsed after α-PD-1 antibody treatment: n = 4) compared to IgG2a-treated tumours (control: n = 4). The data were presented as mean ± S.E.M. and the p-values were assessed by two-tailed unpaired t-test. B Differential gene expression of IFNγ targent genes in short-term melanoma cell cultures derived from ICBT-progressing lesions with elevated IFNγ-signalling compared to cultures where intrinsic IFN-signalling was minimal. Circle area depicts-log₂ fold change and colour intensity depicts-log₁₀(p-value), with ≥1.30 classed as significant. The p-values were assessed by two-tailed unpaired t-test. C GSEA based on RNA-seq data depicting hallmark processes enriched when comparing YUMM2.1 tumours that relapsed after α-PD-1 treatment versus control; and relapsing after α-PD-1 treatment versus responding during α-PD-1 treatment. Circle area depicts the NES, and colour intensity depicts the FDR, with ≤0.25 classed as significant. D–K Bulk-tumour RNA-seq results derived from Untreated (n = 4), PD-1 Responders (n = 4), and PD-1 Progressors (n = 4) analysed by cell-type enrichment analysis (ImmuCellAI), with scores shown for D infiltration, E T cell, F CD8 T cell, G CD8 Tcm, H CD8 Tem, I CD8 Tex, J Macrophage, and K Naive CD8 T cell. The data were presented as mean ± S.E.M. and the adjusted p-values were assessed by one-way ANOVA Šídák’s test. L Expression differences of immunosuppressive gene in tumours derived from α-PD-1-relapsing condition compared with control condition by sequencing bulk mRNA. Circle area depicts-log₂ fold change and colour intensity depicts -log₁₀(p-value), with ≥1.30 classed as significant. The p-values were assessed by two-tailed unpaired t-test. Source data are provided as a Source Data file.