Fig. 1

Correlates of TIGIT DNA methylation with expression and signatures of immune infiltrates, an IFN-γ signature, and T cell activation markers in melanoma. a Genomic organization of the TIGIT gene and analyzed loci. Shown are guanosine/cytosine (GC)-density, the TIGIT consensus transcript, predicted promoter and its flanks, and target sites of HumanMethylation450 BeadChip beads (CpG1-9) and qMSP assay. The modified illustration was exported from www.ensemble.org (Ensembl Release 103) and is based on Genome Reference Consortium Human Build 38 patch release 13 (GRCh38.p13). b Methylation [β values] at nine CpG sites (CpG1-9) and correlation with TIGIT mRNA expression and with histopathologic lymphocyte score according to TCGA [39] (N = 469, TCGA cohort; N = 94, UKB Non-ICB cohort), immunohistochemical TIGIT⁺ lymphocyte score (N = 94, UKB Non-ICB cohort), methylation signature of leukocyte fraction according to Saltz et al. [41] and lymphocyte RNA-Seq signature according to Thorsson et al. [40]. c Spearman’s correlations (Spearman’s ρ) of TIGIT methylation and mRNA expression with RNA-Seq signatures of immune cell infiltrates (resting and activated NK cells, Tregs, T follicular helper cells, naïve CD4⁺ T cells, resting and activated memory CD4⁺ T cells, CD8⁺ T cells, plasma cells, naïve B cells, memory B cells, resting and activated dendritic cells, and M0/M1/M2 macrophages) and their activation status according to Thorsson et al. [40], IFN-γ (INFG, STAT1, STAT2, JAK2, IRF9), and cytotoxic markers (GZMB, PRF1) as well as co-inhibitory markers (PDCD1)