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
