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
Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
Oncoimmunology. 2020 Dec 29;10(1):1856545. 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) 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 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.
胎盘特异性 1（PLAC1）主要在胎盘滋养层细胞中表达，而在正常组织中不表达，由于它是一种癌症睾丸抗原，在各种肿瘤中上调，因此是癌症免疫治疗的一个可靶向候选物。尽管先前已经描述了能够刺激 CD8 T 细胞的肽表位，但尚无关于 PLAC1 CD4 辅助性 T 淋巴细胞（HTL）表位以及该抗原在头颈部鳞状细胞癌（HNSCC）中表达的报道。在此，我们表明 PLAC1 在 74.5%的 HNSCC 患者口咽肿瘤和 51.9%的口腔肿瘤以及几种 HNSCC established 细胞系中高表达。我们还鉴定出一种能够引发有效的抗原特异性和肿瘤反应性 T 细胞应答的 HTL 肽表位（PLAC1）。值得注意的是，该肽表现为一种多反应性表位，能够在不止一种人类白细胞抗原（HLA）-DR 等位基因的背景下刺激 T 细胞，并诱导以 HLA-DR 限制方式杀伤 PLAC1 阳性 HNSCC 细胞系的 PLAC1 特异性 CD4 T 细胞。此外，在 HNSCC 患者的外周血中检测到对 PLAC1 肽有反应的 T 细胞。这些发现表明 PLAC1 代表了 HNSCC 中基于 HTL 的免疫治疗的潜在靶抗原。
