The impact of methylation signatures on cancer cell aggressiveness and cancer-testis antigen specific immunity in head and neck squamous cell carcinoma

Background/State of the art. Cancer-testis antigen (CTA) expression is restricted to germline cells. However, in cancer these embryologic antigens are often reexpressed by promoter demethylation. CTA are immunogenic and attractive targets for specific immunotherapy. MAGE-antigens, PRAME and NY-ESO-1 are the most frequently expressed CTAs in head and neck squamous cell carcinoma (HNSCC) and associated with impaired survival (Laban et al. 2014, Veit et al. 2016). Demethylating agents such as decitabine have been shown to increase CTA expression (Srivastava et al. 2016), which has been implied to improve CTA-specific immunotherapy. On the other hand, decitabine-induced CTA expression may result in increased aggressiveness and reduced prognosis (Zhang et al. 2015). Details of CTA function and their regulation by hypomethylation are poorly characterized to date. Thus it is necessary to evaluate the impact of methylation signatures on the malignant phenotype and CTA specific immunity in HNSCC.