BTLA DNA methylation and mRNA expression in head and neck squamous cell carcinoma

Introduction Due to the success of immunotherapy, several immune checkpoints, such as the immunosuppressive B- and T-Lymphocyte Attenuator (BTLA), are investigated as potential therapeutic targets for therapy of various cancers, including head and neck squamous cell carcinoma (HNSCC). Predictive biomarkers are desperately needed in order to identify patients responding to such treatments. The comprehensive understanding of BTLA regulation on an epigenetic level might provide an avenue in the development of such markers.

Therefore, this study aimed at an extensive investigation of the DNA methylation of BTLA in HNSCC with regard to mRNA expression levels, human papillomavirus (HPV) status, immune cell infiltration, isolated immune cells, and survival.

Materials and methods In addition to BTLA mRNA, methylation at four CpG sites within the BTLA gene in n=528 tumors and n=50 normal adjacent tissues (NAT) from The Cancer Genome Atlas and in isolated immune cells (granulocytes, B cells, CD4+ and CD8+ T cells, and monocytes) were analyzed.

Results BTLA methylation was lower in tumors compared to NAT (p<0.001) and in HPV-negative compared to HPV-positive tumors (p<0.038). Furthermore, we discovered significant correlation of BTLA mRNA expression with CpG methylation within each analysed subset. Additionally, we showed significant methylation differences among distinct immune cells and correlations with RNA-Seq signatures of immune cell infiltrates. High BTLA mRNA expression was associated with a better overall survival.

Conclusion CpG methylation of the BTLA gene locus seems to be an important mechanism in the regulation of BTLA expression and might aid in the development of predictive biomarkers for antagonistic immune checkpoint blockade.

 

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Conflict of Interest

The author declares that there is no conflict of interest.

Publikationsverlauf

Artikel online veröffentlicht:
24. Mai 2022