Identification and application of tumor reactive T cells in hepatobiliary and pancreatic cancers to personalized cancer immunotherapy
| Project/Area Number |
18K08637
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Teikyo University (2019-2021)
National Cancer Center Japan (2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中面 哲也 国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (30343354)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腫瘍浸潤T細胞 / シングル細胞解析 / 疲弊化機構 / TCR導入T細胞 / がん抗原 / ネオアンチゲン / 自己腫瘍反応性 / 非ウイルス性肝細胞がん / TCR遺伝子導入T細胞 / 共通がん抗原 / 腫瘍内浸潤T細胞 / TCR遺伝子 / グリピカン3 / TCR再構築 / トランスクリプトーム解析 / 遺伝子マーカー / 遺伝子治療 / TCR導入T細胞療法 / 肝胆膵領域がん / 自己腫瘍反応性の評価 / TCR遺伝子決定 / ネオアンチゲン予測パイプライン / 腫瘍内免疫環境 / 個別化がん免疫療法 / 腫瘍応答性T細胞 |
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| Outline of Final Research Achievements |
In this project, using single-cell analysis techniques, we successfully identified and characterized tumor reactive CD8+ T cells from surgically resected specimens of hepatobiliary and pancreatic cancers. The patients with tumor reactive CD8+ T cells showed the accumulation of Ki67+ activated CD8+ T cells and the upregulation of genes related with IFNγ signaling pathway in tumor tissue, suggesting that tumor reactive CD8+ T cells isolated in vitro were also associated with immune surveillance in vivo.
We are preparing for the submission of these results. And, we try to examine anti-tumor effects by TCR-T cells with the isolated TCR genes in a patient tumor (PDX) model.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、免疫チェックポイント阻害療法の適応が進むがん治療において、ヒトの腫瘍に浸潤するCD8+T細胞の特徴を調べる方法論を確立し、肝細胞がん、特に非ウイルス性のがんにおいて、腫瘍応答性T細胞の特徴を明らかとした。これらの成果は、肝細胞がんにおける免疫チェックポイント併用療法の効果の理解に繋がるのみならず、自己腫瘍応答性TCR遺伝子を用いたTCR-T細胞療法の開発に繋がると期待されるする。
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Report
(5 results)
Research Products
(16 results)
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[Journal Article] Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer.2021
Author(s)
Oka M, Xu L, Suzuki T, Yoshikawa T, Sakamoto H, Uemura H, Yoshizawa AC, Suzuki Y, Nakatsura T, Ishihama Y, Suzuki A, Seki M
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Journal Title
Genome Biol.
Volume: 22(1):9
Issue: 1
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification.2018
Author(s)
Takahashi D, Kojima M, Suzuki T, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Gotohda N, Ikeda M, Nakatsura T, Ochiai A, Nagino M.
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Journal Title
Sci Rep.
Volume: 8
Issue: 1
Pages: 13166-13166
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Development of a novel personalized immunotherapy targeting common cancer antigen, glypican-3 (GPC3).2021
Author(s)
Charneau Jimmy, Suzuki Toshihiro, Kojima Motohiro, Gothoda Naoto, Takahashi Shinichiro, Sugimoto Motokazu, Suzuki Yutaka, Seki Masahide, Shimomura Manami, Kanaseki Takayuki, Nakatsura Tetsuya
Organizer
第18回日本免疫治療学会学術集会
Related Report
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[Presentation] Analysis of tumor-reactive CTLs and its application to personalized immunotherapy in Hepatobiliary and pancreatic carcinoma2020
Author(s)
Suzuki T, Aazawa Y, Shimizu Y, Yoshikawa T, Kojima M, Gotohda N, Takahashi S, Sugimoto M, Suzuki Y, Seki M, NakatsuraT
Organizer
日本がん免疫学会
Related Report
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