Figure 4. RE hypomethylation is associated with transcriptional reduction of HIF2A expression and increased Immune response.

A EPAS1 (HIF2A) mRNA expression across RE-defined subgroups. Active tumors show significantly lower EPAS1 levels compared with both Repressed and Transient tumors.

B CD8⁺ T cell i C Regulatory T cell (Treg) infiltration estimated from HiTIMED

D Terminal T cell exhaustion scores compared among RE defined Methylation states. E PDCD1 (PD-1) mRNA expression across subgroups. F cGAS–STING activation scores. G Interferon-stimulated gene (ISG) scores, as a proxy for enhanced interferon activity. H Progenitor exhaustion scores.