employing previously defined locations of PMDs and HMDs per 100 kb16, we merged consecutive domains of the same type and retained those >300 kb in length. After assigning average methylation variability and replication timing from normal samples into each merged PMD

mRNA expression of gene Y ~ β1 × global methylation level + β2 × mutation burden + β3 × aneuploidy level + β4 × tumour purity + β5 × age + β6 × tumour stage

This is the first study that inspected DNA methylation patterns in the molecular and clinical data with regards to cancer immunotherapy. As a result, we suggest that as an important predictive marker in immunotherapy, genomic demethylation implicates epigenetic modulation as a combination regimen for precision immunotherapy.

In particular, antibody-mediated interventions targeting cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1) on T lymphocytes and the principal ligand (PD-L1) on tumour cells can reverse tumour-induced immunosuppression and induce durable clinical responses1.

Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort ( n = 60) and a published cohort ( n = 81) in lung cancer and a melanoma cohort ( n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden... See more