Diversity and shared T‑cell receptor repertoire analysis in esophageal squamous cell carcinoma

Sudo,Tomoya; Kawahara,Akihiko; Ishi,Kazuo; Mizoguchi,Atsushi; Nagasu,Sachiko; Nakagawa,Masashi; Fujisaki,Masahiro; Hino,Haruhiro; Saisho,Kouhei; Kaku,Hideaki; Matono,Satoru; Mori,Naoki; Akiba,Jun; Yamada,Akira; Akagi,Yoshito

doi:10.3892/ol.2021.12879

Diversity and shared T‑cell receptor repertoire analysis in esophageal squamous cell carcinoma

Authors:
- Tomoya Sudo
- Akihiko Kawahara
- Kazuo Ishi
- Atsushi Mizoguchi
- Sachiko Nagasu
- Masashi Nakagawa
- Masahiro Fujisaki
- Haruhiro Hino
- Kouhei Saisho
- Hideaki Kaku
- Satoru Matono
- Naoki Mori
- Jun Akiba
- Akira Yamada
- Yoshito Akagi
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Affiliations: Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Hospital Diagnosis, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Biostatistics Center, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Cancer Vaccine Development Division, Research for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
Published online on: June 24, 2021 https://doi.org/10.3892/ol.2021.12879
Article Number: 618
Copyright: © Sudo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The tumor immune response is dependent on the interaction between tumor cells and the T‑cell subset expressing the T‑cell receptor (TCR) repertoire that infiltrates into the tumor microenvironment. The present study explored the diversity and shared TCR repertoires expressed on the surface of locoregional T cells and identified the T lymphocyte subsets infiltrating into esophageal squamous cell carcinoma (ESCC), in order to provide insight into the efficiency of immunotherapy and the development of a novel immune‑oriented therapeutic strategy. A total of 53 patients with ESCC were enrolled in the present study, and immunohistochemical analysis of CD3, CD8, CD45RO, FOXP3, CD274, HLA class I and AE1/AE3 was performed. Digital pathological assessment was performed to evaluate the expression level of each marker. The clinicopathological significance of the immuno relation high (IR‑Hi) group was assessed. Adaptor ligation PCR and next‑generation sequencing were performed to explore the diversity of the TCR repertoire and to investigate the shared TCR repertoire in the IR‑Hi group. Repertoire dissimilarity index (RDI) analysis was performed to assess the diversity of TCR, and the existence of shared TCRα and TCRβ was also investigated. Further stratification was performed according to the expression of markers of different T‑cell subsets. Patients were stratified into IR‑Hi and immuno relation low (IR‑Lo) groups. Cancer‑specific survival and recurrence‑free survival rates were significantly improved in the IR‑Hi group compared with in the IT‑Lo group. The diversity of the TCR repertoire was significantly higher in the IR‑Hi group. TCR repertoire analysis revealed 27 combinations of TCRα and 23 combinations of TCRβ VJ regions that were shared among the IR‑Hi group. The IR‑Hi group was divided into three clusters. Overall, the current findings revealed that the IR‑Hi group maintained the diversity of TCR, and a portion of the IR‑Hi cases held the T cells with shared TCR repertoires, implying recognition of shared antigens. The prognosis of patients with ESCC was affected by the existence of immune response cells and may possibly be stratified by the T‑cell subsets.

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