Lower CTLA-4 methylation in melanoma samples indicated a better response to anti-PD1 or anti-CTLA-4 therapy [131] and increased level of PD-1, CTLA-4, or PD-L1 was found to correlate with DNA hypomethylation across many types of tumors such as non-small cell lung cancer, lower grade gliomas (LGG), and head and neck squamous cell carcinoma [132]. This evidence concerns the gene CTLA4 and head and neck squamous cell carcinoma.