Fig. 5: Enrichment of HERV-specific T cells in patients correlates with enhanced expression of HERV elements.

RNA-seq analysis of previously published data of 18 patients from the Australian patient cohort was performed to quantify the expression of the 49 HERVs tested for T cell analysis. a Expression of the 49 HERVs in each of the patients (before, n = 18, and after, n = 16, AZA treatment) compared with healthy donors (n = 14). Mann–Whitney–Wilcoxon test, two-tailed, p < 2.2e−16 (healthy donors vs pre-AZA), p < 2.2e−16 (healthy donors vs post--AZA). Wilcoxon Signed-Rank test, two-tailed, p = 1.8e−4 (pre-AZA vs post-AZA). RNA-seq data of healthy donors were obtained from previously published data (Supplementary Table 6). Healthy donors, n = 588 (49 HERVs across 12 healthy donors; pre- and post-AZA, n = 784 (49 HERVs across 16 patients). b Correlation of HERV-specific T cell responses identified in patient samples (shown in Fig. 2) with the expression of their associated HERVs. X-axis shows expression of the HERV transcripts (mean across the 18 patients, before or after treatment). Y-axis shows the proportion of identified T cell epitopes (before and after AZA treatment), i.e., number of T cell epitopes detected out of total predicted epitopes from a given HERV. Spearman correlation between HERV expression and T cell responses, r = 0.47 was significantly different from zero (p = 0.018) (source data are provided as Source data file). c Expression of the 18 HERV loci recognized by T cell populations compared with the expression of the 31 HERV loci not contributing to any T cell response. Expression was quantified as transcripts per million of total reads (TPM) and is given as the mean value for patients, including values both before and after AZA treatment; Mann–Whitney–Wilcoxon test, two-tailed, p = 0.26. T cell positive, n = 18; T cell negative, n = 31 (source data are provided as Source data file). d Heatmap of estimated fold change for individual HERVs across the 18 patients (before treatment) compared to mean expression HERV value across all healthy donors (using mean expression values of transcripts for each HERV gene). For comparative representation, the fold change color scale is restricted from −6 to 6, and fold change values outside this limit are shown at the maximum (>6 = 6) or minimum scale (< −6 = −6). HERV specific T cell occurrence together with information regarding clinical response is annotated in the top bars for each patient. e Similar to (d) comparing pre- and post-AZA treatment. In boxplots the box shows the 1st quartile (Q1), the median, and the 3rd quartile (Q3), while whiskers extend to 1.5 times the interquartile range (IQR) on either side of the box (or to the minimum and maximum data values if these are less than 1.5 * IQR from Q1 and Q3).