The Potential of DNA Methylation of Immune Checkpoint Genes as Predictive Biomarker for Immunotherapies

The success of immunotherapies with monoclonal therapeutic antibodies targeting PD-1 recently resulted in the regulatory approval for treatment of recurrent or metastatic head and neck squamous cell carcinomas (HNSCC). However, only a portion of patients responds to this immune checkpoint blockade while non-responding patients could benefit from chemotherapy or targeted therapy instead. This results in a high clinical need for predictive biomarkers which allow for the preceding identification of patients who are likely to respond in order to adapt the therapy accordingly. DNA methylation of CpG-dinucleotides is an epigenetic mechanism which plays a fundamental role within various processes, e.g. carcinogenesis and differentiation. We performed a detailed analysis of DNA methylation of the immune checkpoint genes PD-1, PD-L1, PD-L2, and CTLA-4 in HNSCC. Depending on the sequence context of the analyzed CpG we found significant correlations and associations with gene expression, immune cell infiltrates, human papillomavirus (HPV) status, mutational load, overall survival, and progression-free survival in patients treated with anti-PD-1 immune checkpoint blockade. DNA methylation of immune checkpoint genes therefore represents a promising candidate for the development of predictive biomarkers for immunotherapies.

Poster-PDF A-1302.pdf

Conflict of interest

Der Erstautor gibt keinen Interessenskonflikt an.

Publication History

Article published online:
13 May 2021