Tumor-promoting function of paternally expressed gene 10 and its immunogenicity in inducing anti-tumor helper T cells...

Paternally expressed gene 10 (PEG10) is expressed primarily in the placenta; its expression is extremely low or absent in normal tissues but up-regulated in various cancers, indicating that PEG10 is a potential target for cancer immunotherapy. However, the expression and role of PEG10 in head and neck squamous cell carcinoma (HNSCC) and the immunogenicity of possible PEG10-derived T-cell epitopes remain unclear. In the present study, we show that PEG10 is expressed in HNSCC, and its high expression is associated with poor patient survival. Suppression of PEG10 expression attenuated the proliferation, migration, and invasion of HNSCC cells and altered their gene expression profiles. We also identified a PEG10-derived peptide epitope (PEG10_216-232) capable of eliciting antigen-specific and promiscuous human leukocyte antigen (HLA)-DR-restricted helper T lymphocyte (HTL) responses. Notably, PEG10-specific HTLs exerted direct cytotoxicity against PEG10-positive HNSCC cells in an HLA-DR-restricted manner. Moreover, precursor T cells that react to PEG10_216-232 peptide were detected in HNSCC patients. These results indicate that PEG10 plays an important role in HNSCC tumorigenesis and qualifies as an immunotherapeutic target against HNSCC. The helper epitope peptide of PEG10 could effectively stimulate antigen-specific HTLs and induce anti-tumor responses against PEG10-positive cancers, including HNSCC.