In a tumor model, de novo methylation at the Tcf7 and Ccr7 loci occurs in PD-1hi tumor infiltrating lymphocytes (TILs) relative to PD-1lo TILs, suggesting that exhaustion within the TME is associated with the adoption of methylation programs that in part target these key loci associated with the precursor exhausted state [55]. The gene discussed is CCR7; the disease is neoplasm.