CD27 mRNA expression and promoter DNA methylation in head and neck squamous cell carcinoma

Introduction The tumor necrosis factor receptor superfamily member 7 (TNFRSF7, also known as CD27) is an immune checkpoint that is currently investigated as a target for immunotherapy of cancers, including head and neck squamous cell carcinomas (HNSCCs). A comprehensive understanding of the CD27 regulation, in particular on an epigenetic level, might aid in the development of companion predictive biomarkers.

This study aimed at the detailed investigation of the DNA methylation of CD27 in HNSCC with regard to mRNA expression levels, human papillomavirus (HPV) status, immune cell infiltration, and survival.

Materials and methods We analyzed methylation of five CpG sites within the central promoter of CD27 in subsets of isolated immune cells (B cells, CD4+ and CD8+ T cells, monocytes, granulocytes) from peripheral blood and in n=521 tumors and n=50 normal adjacent tissues from The Cancer Genome Atlas.

Results CD27 mRNA expression is significantly higher in HPV-positive compared to HPV-negative tumors and showed a significant inverse correlation with promoter CpG methylation. We showed significant DNA methylation differences among subsets of immune cells and significant correlations with RNA-Seq signatures of distinct immune infiltrates. High CD27 mRNA tumor levels were significantly associated with better overall survival.

Conclusion Our findings suggest an epigenetic regulation of CD27 via CpG methylation in the HNSCC tumor microenvironment and might aid in the development of predictive biomarkers for agonistic immune checkpoint blockade.

Publication History

Article published online:
24 May 2022