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PD-1, CTLA4, PD-L1 and PD-L2 DNA methylation in papillary thyroid carcinoma.

Aim: We investigated DNA methylation patterns of immune checkpoint genes PD-1, PD-L1, PD-L2, CTLA4 and an adjacent long noncoding RNA in papillary thyroid carcinoma (PTC). Materials & methods: DNA methylation and mRNA expression were examined in PTCs. DNA methylation was correlated with mRNA expression, BRAF and RAS mutational status, and immune cell infiltration. Results: Inverse correlations between DNA methylation and mRNA expression were observed. Immune checkpoint expression correlated positively, and DNA methylation negatively, with immune cell infiltration. Higher DNA methylation levels accompanied by lower immune checkpoint expression were observed in RAS-mutated tumors. Conclusion: We suggest epigenetic regulation of immune checkpoints in PTC. Methylation was associated with BRAF and RAS mutation status. DNA methylation might be a promising biomarker candidate in the context of immunotherapies in PTC.