Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma

• Published in: Oncoimmunology 2021-01, Vol.10 (1), p.1856545-1856545
• Main Authors: Hayashi, Ryusuke, Nagato, Toshihiro, Kumai, Takumi, Ohara, Kenzo, Ohara, Mizuho, Ohkuri, Takayuki, Hirata-Nozaki, Yui, Harabuchi, Shohei, Kosaka, Akemi, Nagata, Marino, Yajima, Yuki, Yasuda, Syunsuke, Oikawa, Kensuke, Kono, Michihisa, Kishibe, Kan, Takahara, Miki, Katada, Akihiro, Hayashi, Tatsuya, Celis, Esteban, Harabuchi, Yasuaki, Kobayashi, Hiroya
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - genetics; CD4 T cells; epitope; Epitopes, T-Lymphocyte - genetics; Female; Head and Neck Neoplasms - genetics; head and neck squamous cell carcinoma; helper T lymphocytes; Humans; immunotherapy; Male; Original Research; peptide vaccine; PLAC1; Placenta; Placenta-specific 1; Pregnancy; Pregnancy Proteins; Squamous Cell Carcinoma of Head and Neck - genetics; T-Lymphocytes, Helper-Inducer
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2020.1856545

Placenta-specific 1 (PLAC1) is expressed primarily in placental trophoblasts but not in normal tissues and is a targetable candidate for cancer immunotherapy because it is a cancer testis antigen known to be up-regulated in various tumors. Although peptide epitopes capable of stimulating CD8 T cells have been previously described, there have been no reports of PLAC1 CD4 helper T lymphocyte (HTL) epitopes and the expression of this antigen in head and neck squamous cell carcinoma (HNSCC). Here, we show that PLAC1 is highly expressed in 74.5% of oropharyngeal and 51.9% of oral cavity tumors from HNSCC patients and in several HNSCC established cell lines. We also identified an HTL peptide epitope (PLAC1 31-50 ) capable of eliciting effective antigen-specific and tumor-reactive T cell responses. Notably, this peptide behaves as a promiscuous epitope capable of stimulating T cells in the context of more than one human leukocyte antigen (HLA)-DR allele and induces PLAC1-specific CD4 T cells that kill PLAC1-positive HNSCC cell lines in an HLA-DR-restricted manner. Furthermore, T-cells reactive to PLAC1 31-50 peptide were detected in the peripheral blood of HNSCC patients. These findings suggest that PLAC1 represents a potential target antigen for HTL based immunotherapy in HNSCC.