TCR repertoire analysis in esophageal cancer
Project/Area Number |
16K07130
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Tumor biology
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Research Institution | Kurume University |
Principal Investigator |
Sudo Tomoya 久留米大学, 医学部, 助教 (50309803)
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Co-Investigator(Kenkyū-buntansha) |
山田 亮 久留米大学, 付置研究所, 教授 (50158177)
三森 功士 九州大学, 大学病院, 教授 (50322748)
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Research Collaborator |
Mizoguchi Atsushi
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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Keywords | 食道癌 / T細胞サブセット / 包括的TCR解析 / 食道扁平上皮癌 / TCR解析 / TIL / T細胞 / サブセット / T cell subset / 炎症とがん |
Outline of Final Research Achievements |
The purpose of this study is to unveil the subset pattern of T-lymphocytes and the common TCR repertoire in esophageal cancer. Fifty-three cases were enrolled and immunohistochemical staining was performed using CD3/CD8/CD45RO/Foxp3/PD-L1/HLA and AE1/AE3 antibodies. Digital scan and quantification was performed. The clinicopathological significance of CD3-Hi group and further stratification was tested using other T cell subset markers. Adaptor ligation PCR with next generation sequencing was performed to explore the common TCR repertoire in CD3-Hi group. Patients were stratified into CD3 high expression (CD3-Hi) group and CD3 low expression (CD3-Lo) group. Overall survival and disease free survival were significantly better in CD3-Hi group. CD3-Hi group was divided into three clustering groups. In the TCR repertoire analysis there was a total of 29 combinations of TCRα TRAV|TRAJ and 52 combinations of TCRβ TRBV|TRBJ recombination repertoires significantly amplified in CD3-Hi group.
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Academic Significance and Societal Importance of the Research Achievements |
食道癌の局所には異なるT細胞サブセットが存在し、免疫チェックポイント阻害剤(ICI)を使用する際にはこのT細胞のパターンを考慮して導入する必要があることが明らかになった。また、T細胞には共通のTCRレパートリーが存在する可能性があることも明らかとなった。本研究では、TCRのレパートリー内でアミノ酸配列についてのマッチングも検討を行ったが、一致するものは認められなかった。事前に予想されていたことであったが、TCR解析をより詳細に行うことで、個人個人に合わせた至適な免疫治療の開発につながる可能性があり、本研究が明らかにした結果は免疫治療の至適化という点で少なからず意義はあったと考えられる。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Clinical Impact of Tumor-Infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma.2017
Author(s)
Sudo T, Nishida R, Kawahara A, Saisho K, Mimori K, Yamada A, Mizoguchi A, Kadoya K, Matono S, Mori N, Tanaka T, Akagi Y.
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Journal Title
Ann Surg Oncol.
Volume: in press
Issue: 12
Pages: 3763-3770
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] The Analysis of T Cell Subsets, PD-L1 and HLA Expression in Esophageal Squamous Cell Carcinoma2018
Author(s)
Tomoya Sudo, Takato Yomoda1, Sachiko Nagasu, Kouhei Saisho, Yuya Tanaka, Keizou Yamaguchi, Hidefumi Nogita, Haruhiro Hino, Naoki Mori, Satoru Matono, Toshiaki Tanaka, Tetsushi Kinugasa, Yoshito Akagi
Organizer
日本消化器外科学会
Related Report
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[Presentation] The analysis of the expression pattern of immune checkpoint molecules and the subset of T lymphocytes in locoregional esophageal squamous cell carcinoma2018
Author(s)
Tomoya Sudo, Takato Yomoda, Saisho Kouhei, Takahiro Shigaki,Taizan Minami, Yuya Tanaka, Hideaki Kaku, Hiroyuki Nakane, Matono Satoru, Mori Naoki, Tanaka Toshiaki , Akagi Yoshito
Organizer
日本癌学会
Related Report
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[Presentation] Locoregional T cell subset analysis in Esophageal Squamous Cell Carcinoma2018
Author(s)
Tomoya Sudo, Kawahara Akihiko, Haruhiro Hino, Yuya Tanaka, Hideaki Kaku, Hiroyuki Nakane, Saisho Kouhei, Taizan Minami, Matono Satoru, Mori Naoki, Tanaka Toshiaki, Mimori Koshi, Yamada Akira, Akagi Yoshito
Organizer
日本癌治療学会
Related Report
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[Presentation] PDL1 expression and tumor infiltrating lymphocyte subset analysis in primary esophageal cancer tissue2017
Author(s)
Tomoya Sudo, Mizoguchi Atsushi, Kawahara Akihiko, Haruhiro Hino, Saisho Kouhei, Nagasu Sachiko, Taizan Minami, Matono Satoru, Mori Naoki, Tanaka Toshiaki, Mimori Koshi, Yamada Akira, Akagi Yoshito
Organizer
日本癌学会
Related Report
Int'l Joint Research
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[Presentation] Trial of Analysis The Expression of PDL1 Expression and The Subset of Tumor Infiltrating Lymphocyte in Esophageal Squamous Cell Carcinoma2017
Author(s)
Tomoya Sudo, Mizoguchi Atsushi, Kawahara Akihiko, Haruhiro Hino, Saisho Kouhei, Nagasu Sachiko, Taizan Minami, Matono Satoru, Mori Naoki, Nanaka Toshiaki, Mimori Koshi, Yamada Akira, Akagi Yoshito
Organizer
日本癌治療学会
Related Report
Int'l Joint Research
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