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

Immunotherapy
Luka de VosAlina Franzen

Abstract

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.

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Citations

Aug 13, 2021·Thyroid : Official Journal of the American Thyroid Association·Siyuan WanHongmei Shen

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Datasets Mentioned

BETA
AC131097.3

Methods Mentioned

BETA
RNASeq
methylation profiling

Clinical Trials Mentioned

NCT02973997
NCT03246958
NCT03181100

Software Mentioned

Ensembl
R package ‘ methylumi ’
SPSS

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