Fig. 3: HLA-A transcript downregulation associated with markers of de-differentiation.

a Scatter plot showing the Pearson correlation coefficient of CYT score with the expression of MHC class I genes, HLA-A, -B, -C and B2M in responding (RES; n = 6), and pre-treatment (PRE; n = 44) and progressing biopsies (PROG; n = 29). b Plots showing expression of HLA-A and SNAI1 in the CYT score-matched tumors (n = 38) with high or low HLA-A transcript expression. FDR-adjusted p-values (q) calculated using limma test. The HLA-A low melanoma tumor derived from patient 53 was found to express a STAT1^S316L mutation (highlighted). c Heat map showing differentially expressed genes (FDR adjusted p-value < 0.001 are shown) between CYT score-matched tumors (n = 38) with low or high HLA-A transcript expression. CYT score is also shown and HLA-A, SNAI1 and NGFR genes are highlighted. Best irRC response is also shown. d Correlation matrix of SNAI1 gene expression with ssGSEA scores derived from the Hallmark gene set collection and stromal cell-specific transcriptome signatures^25,26 in 79 melanoma biopsies. The Spearman rank correlation coefficients are shown within the matrix, and the false discovery adjusted p-value was <0.01 for all signatures shown (see Supplementary Data 7). e Subset of top scoring genesets (GSEA PreRanked; Hallmark gene set collection and stromal cell-specific transcriptome signatures^25,26) upregulated in the tumors with low HLA-A transcript expression compared to HLA-A high expressing tumors.