Table 1 Top ranked immunological transitions of melanoma progression

Upregulated (> 2fc) in both primary and metastatic melanoma compared to normal melanocyte (Immunological relevance score for each gene (KL) > 11 bits).

CD4, IL10, CD8A, CD40, IL15, IL7, IL18, TNFSF13B, PTPRC, IL13RA2, IL1A, PECAM1, C5AR1, CD86, ISG20, IL18R1, CD14, ITGB2, ADORA3, FCGR3A, CCL2, IL8, CCR5, FCGR3B

Signatures of T-cell infiltration, T-cell activation and the inflammatory response. Inclusive of the Th1 inhibiting cytokines

Downregulated (> 2fc) in both primary and metastatic melanoma compared to normal melanocyte (Immunological relevance score for each gene (KL) > 0.5 bits).

MME, IL24, DPP4, CYGB, MSC, SLC7A8

Regulation of extracellular matrix (ECM) remodeling, through proteolytic enzymes, and amino acid transporters

Upregulated (> 2fc) in primary melanoma compared to normal melanocyte. Not subject to >2fc in metastasis (Immunological relevance score for each gene (KL) > 2 bits).

IL5, TNF, IL1RN, DARC, HLA-DRB4, CFP, PTPN6, CD1B, ELA2, IL17B, ATP8A2, SLPI, CD27, STAT4, CDA, IL26, DEFB4, NFKBIA, HRH1, XCL1, DEFB1, PDPN, CTSG, SDC1, GATA3, MSMB, CD24, POU1F1, PRDM1, EBF1

Cytokine activity that is pro-survival and towards ECM remodeling. Increased transcriptional activity related to T-cell activation in the primary tumor. Increased presence of MHC class II markers.

Downregulated (> 2fc) in primary melanoma compared to normal melanocyte. Not subject to >2fc in metastasis (Immunological relevance score for each gene (KL) > 1 bit).

BAX, TNFRSF10B, SV2A

Down-regulation is indicative of p53 dysfunction and transduction of apoptosis signals. Overall leading to pro-survival in the primary tumor compared to normal cells

Upregulated (> 2fc) in metastatic melanoma compared to normal melanocyte. Not subject to >2fc in primary. (Immunological relevance score for each gene (KL) > 1 bit).

CCRL2, HLA-DRB1, MDK, C4A, CD55, CD80, FCGR1A, KLRC4, ICAM1, SPI1, HCST, PPBP, FCGR2C, GPR160, CXCL16, FOS, SERPINA1

Mediators of inflammation, angiogenesis, cell growth, and cell migration. Also present are signals of humoral immunity in the form of T-cell activation and B-cell development genes

Downregulated (> 2fc) in metastatic melanoma compared to normal melanocyte. Not subject to >2fc in primary. (Immunological relevance score for each gene (KL) > 1 bit).

KIT, IRF4, MLANA, MMP1

Down regulation of cell adhesion, differentiation factors and regulators of the innate and adaptive immune systems. Possibly promoting the metastatic phenotype

Upregulated (> 2fc) in metastatic melanoma compared to primary (Immunological relevance score for each gene (KL) < 1 bit).

MAGEA3, CSAG2, MAGEA2, GAGE1, MAGEA12, GAGE3, FKBP10

Eliciting immune T cell activation in metastatic tumors, as a consequence of being expressed particularly in the metastatic stages, while having very restricted expression in normal cells

Downregulated (> 2fc) in metastatic melanoma compared to primary (Immunological relevance score for each gene (KL) > 1 bit).

S100A9, S100A8, SLPI, DEFB4, DEFB1, MSMB, CD24, DEFB103A, COL17A1

Altered matrix remodeling and migratory behavior. Dynamic changes in the (ECM) in the metastatic tumors. Inclusive in this is the down regulation of important chemoattractants of innate immune cells