Functional analysis of novel immune checkpoints and development of combined immunotherapy in gynecological cancer
Project/Area Number |
19K09832
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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 |
Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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Research Institution | Keio University |
Principal Investigator |
Nishio Hiroshi 慶應義塾大学, 医学部(信濃町), 講師 (90445239)
|
Co-Investigator(Kenkyū-buntansha) |
岩田 卓 慶應義塾大学, 医学部(信濃町), 講師 (30296652)
谷口 智憲 慶應義塾大学, 医学部(信濃町), 講師 (40424163)
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
Keywords | 卵巣癌 / がん免疫療法 / がん微小環境 / 免疫寛容 / 卵巣がん / 制御性T細胞 / immunotherapy / regulatory Tcell / ovarian cancer / immunoescape / 免疫療法 / 免疫逃避 / 免疫チェックポイント |
Outline of Research at the Start |
本研究では婦人科がんにおけるがん免疫病態の解明と申請者らが新たに同定した分子Neuritin1(Nrn1)の機能解明に基づく新たな免疫療法の開発を目指す.具体的には婦人科がん臨床検体サンプルおよび腫瘍モデルマウスを用いて,Nrn1の卵巣がん組織を中心とした婦人科がん組織での発現を確認する.さらにNrn1のがん免疫環境における機能解析と治療ターゲットとしての検討実験を,Nrn1ノックアウトマウスを含めたin vitro/in vivoの方法で検討し,Nrn1のがん免疫療法としての治療ターゲットの妥当性を検討し,最終的にはそれらの結果を統合して新たな複合的免疫療法を確立することを目的とする.
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Outline of Final Research Achievements |
We analyzed the function of Neuritin1 (Nr1), which is specifically expressed on regulatory T cells (Treg) in the cancer microenvironment. Tumors transplanted into Nrn1KO mice showed less tumor growth than those transplanted into WT mice. The number of tumor-infiltrating Tregs was also suppressed. The RNA sequence analysis of Nrn1 showed that Nrn1 was linked to the expression status of Treg-related genes, suggesting that Nrn1 is an important molecule for the induction and maintenance of regulatory T cells. Nrn1 is thought to be an important molecule for the induction and maintenance of regulatory T cells.
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Academic Significance and Societal Importance of the Research Achievements |
チェックポイント阻害剤が臨床効果を認めるという点やCD8+T 細胞を中心とした免疫病態には個体差があること,また個体差が免疫療法のみならず手術・化学療法などの標準治療の反応性にも関与することが報告されている.しかしこれらの機序の解明についてはまだ不明なことが多く,免疫病態を制御するための新たな治療標的の同定や治療薬の開発は遅れているのが現状である.今回新たに同定したNrn1 をターゲットとしたがん免疫療法はこれまで世界で報告がなく,本研究は極めて高い学術的独自性を有している.またNrn1 が治療標的としての効果が確認されれば,婦人科がんのみならず様々ながん腫に応用が拡がる可能性がある.
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Transcription Factor Homeobox D9 Drives the Malignant Phenotype of HPV18-Positive Cervical Cancer Cells via Binding to the Viral Early Promoter2021
Author(s)
Hayashi S, Iwata T, Imagawa R, Sugawara M, Chen G, Tanimoto S, Sugawara Y, Tanaka I, Matsui T, Nishio H, Nakamura M, Katoh Y, Mori S, Kukimoto I, Aoki D.
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Journal Title
Cancers (Basel)
Volume: 13(18)
Issue: 18
Pages: 4613-4613
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Tumor-infiltrating lymphocytes predict survival outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy2020
Author(s)
Akiko Ohno, Takashi Iwata, Yuki Katoh, Shiho Taniguchi, Kohsei Tanaka, Hiroshi Nishio, Masaru Nakamura , Tohru Morisada, Guanliang Chen, Miyuki Saito, Tomonori Yaguchi, Yutaka Kawakami, Daisuke Aoki
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Journal Title
Gynecol Oncol .
Volume: 159
Issue: 2
Pages: 329-334
DOI
Related Report
Peer Reviewed
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[Journal Article] Transcription factor homeobox D9 is involved in the malignant phenotype of cervical cancer through direct binding to the human papillomavirus oncogene promoter2019
Author(s)
Hirao N, Iwata T, Tanaka K, Nishio H, Nakamura M, Morisada T, Morii K, Maruyama N, Katoh Y, Yaguchi T, Ohta S, Kukimoto I, Aoki D, Kawakami Y.
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Journal Title
Gynecol Oncol
Volume: 155
Issue: 2
Pages: 340-348
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] A novel checkpoint molecule, neurotrophic factor X, is a promising immunotherapy target for ovarian cancer.2019
Author(s)
Nishio Hiroshi, Iwata Takashi, Tanaka Kohsei, Saiki Naohiko, Nishio Sakiko, Nakamura Masaru, Morisada Tohru, Tanaka Mamoru, Aoki Daisuke.
Organizer
第71回日本産科婦人科学会学術講演会
Related Report