In particular, naïve higher expression levels (hypomethylation) in tumor necrosis factor receptors OX40 (TNFRSF4) and GITR (TNFRSF18, AITR) appear to be significantly associated with improved OS in HNSCC patients, whereas higher methylation levels of CpG5-7 (downregulation from GITR), CpG13-21 (GITR promoter), intergenic CpG31-32, and CpG42 (OX40 promoter) are highly associated with worse survival outcomes [50]. The gene discussed is TNFRSF4; the disease is head and neck squamous cell carcinoma.