Fig. 1

Epigenetic and transcriptomic analysis of T cell in childhood cancer survivors (CCS). a. No difference in global DNA methylation was observed in total lymphocytes or B cells (CD3⁻CD21⁺) between CCS who received total body irradiation and hematopoietic stem cell transplant (TBI/HSCT) compared to those who received no irradiation (non-IRR, p > 0.05). CD4⁺ cells from CCS treated with TBI/HSCT showed global hypomethylation (p = 0.05), with a similar trend in CD8⁺ cells (p = 0.07), whereas monocytes tended to show hypermethylation (p = 0.06). b. Volcano plot representing the distribution of differentially methylated genes in the two groups of survivors, with more than 400 genes differentially methylated (represented in red, with a difference in methylation of more than 25%). c. Sankey diagram showing representative Gene Ontology (GO) terms clusters from differentially methylated genes, including all main GO terms related to immunological processes or oxidative stress. The width of the arrow is proportional to the contribution of the gene to the GO term and to the contribution of the GO term to immunological processes or oxidative stress d. Volcano plot reflecting the distribution of differentially expressed genes (in red) between the two groups of CCS. e. Representative GO terms clusters from differentially expressed genes showed a particular enrichment in GO terms related to immune processes and oxidative stress. f. Predicted biological age based on methylation levels on three specific CpG sites on ASPA, ITGA2B, and PDE4C was higher in CCS treated with TBI/HSCT. Both groups showed increased distance from the regression line, suggesting increased biological predicted age compared to chronological age. Chronological age was not different between the donors and the children who received hematopoietic stem cells transplant at the time of the experiment (p > 0.05)