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

Ryusuke Hayashi, Toshihiro Nagato, Takumi Kumai, Kenzo Ohara, Mizuho Ohara, Takayuki Ohkuri, Yui Hirata-Nozaki, Shohei Harabuchi, Akemi Kosaka, Marino Nagata, Yuki Yajima, Syunsuke Yasuda, Kensuke Oikawa, Michihisa Kono, Kan Kishibe, Miki Takahara, Akihiro Katada, Tatsuya Hayashi, Esteban Celis, Yasuaki HarabuchiHiroya Kobayashi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 (PLAC131-50) 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 PLAC131-50 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.

Original languageEnglish (US)
Article number1856545
JournalOncoImmunology
Volume10
Issue number1
DOIs
StatePublished - 2021

Keywords

  • CD4 T cells
  • PLAC1
  • Placenta-specific 1
  • epitope
  • head and neck squamous cell carcinoma
  • helper T lymphocytes
  • immunotherapy
  • peptide vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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