Extended Data Fig. 10 |. Analysis of HLA class II expression in cancer cell lines.

a, Tumor mutation burden (top panel) with HLA class I and HLA class II expression scores (middle and bottom panels) of 927 human cancer cell lines²². HLA class I and II scores have been calculated from RNAseq as described in the Material and Methods section. Colored areas denote downregulation of HLA class I (turquoise) and upregulation of HLA class II (pink). Each tumor type is indicated using the corresponding abbreviation from TCGA (x axis). The number of tested cancer cell lines for each tumor type is reported (top). Bars depict mean values with s.d. Compared to hematopoietic tumors, melanoma (SKCM) represents the sole solid cancer with a relevant number of HLA class IIp^os cell lines (red arrow). b, Volcano plot showing RNA transcripts deregulated upon comparison of HLA class IIp^os (n = 18) and HLA class II^neg (n = 36) melanoma cell lines (Mel-CLs). Significantly upregulated or downregulated genes (log2FC≥ 2 or log2FC≤ −2, adj-p.value ≤ 0.01) are colored in red or blue respectively. HLA class II related genes are labeled; Upregulated genes previously associated with de-differentiated melanoma^23,24,47 are highlighted in green. c, Top 20 gene ontology processes enriched in transcripts upregulated in HLA class IIp^os Mel-CLs. HLA class II related genes were excluded from this analysis. Bars depict enrichment, as calculated using two-sided Fisher’s exact test⁴⁸. Processes related to differentiation of central nervous system are colored in green, while processes related to remodeling of interactions with cells or extracellular matrix are highlighted in yellow. Enrichment in such gene- ontologies, characteristic of neural-crest-like tumors^23,24,47, in HLA class IIp^os melanoma confirm that HLA class II expression is peculiar of de-differentiated melanoma. No significant deregulation of genes derived from HLA class II RNA- interference screens⁴⁹ was observed.