徳島大学 教育・研究者情報データベース(EDB)

1. (英) Sugimoto Koji

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2. 前川 洋一

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3. 北村 明子

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4. 西田 純

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5. (英) Koyanagi Akemi

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6. (英) Yagita Hideo

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7. (英) Kojima Hidefumi

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8. (英) Chiba Shigeru

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9. 島田 光生([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.外科系.消化器・移植外科学])

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10. 安友 康二([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.病理系.生体防御医学])

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(英) Notch2 signaling is required for potent antitumor immunity in vivo.

(英) CD8(+) T cells play a central role in cancer immunosurveillance, and the efficient induction of CTLs against tumor Ags is required for successful immunotherapy for cancer patients. Notch signaling directly regulates the transcription of effector molecules in CTLs. However, it remains unclear whether Notch signaling in CD8(+) T cells is required for antitumor CTL responses and whether modulation of Notch signaling can augment antitumor CTL responses. In this study, we demonstrate that signaling by Notch2 but not Notch1 in CD8(+) T cells is required for antitumor CTL responses. Notch2(flox/flox) mice crossed with E8I-cre transgenic (N2F/F-E8I) mice, in which the Notch2 gene is absent only in CD8(+) T cells, die earlier than control mice after inoculation with OVA-expressing EG7 thymoma cells. In contrast, Notch1(flox/flox) mice crossed with E8I-cre transgenic mice inoculated with EG7 cells die comparable to control mice, indicating that Notch2 is crucial for exerting antitumor CTL responses. Injection of anti-Notch2 agonistic Ab or delta-like 1-overexpressing dendritic cells augmented the antitumor response in C57BL/6 mice inoculated with EG7 cells. These findings indicate that Notch2 signaling in CD8(+) T cells is required for generating potent antitumor CTLs, thus providing a crucial target for augmenting tumor immune responses.

1. (英) Animals
2. (英) Antibodies, Monoclonal
3. (英) CHO Cells
4. (英) Cell Line, Tumor
5. (英) Cells, Cultured
6. (英) Cricetinae
7. (英) Cricetulus
8. (英) Growth Inhibitors
9. (英) Immunotherapy, Adoptive
10. (英) Mice
11. (英) Mice, Inbred C57BL
12. ノックアウトマウス(knockout mice)
13. (英) Mice, Transgenic
14. (英) Receptor, Notch1
15. (英) Receptor, Notch2
16. シグナル伝達(signal transduction)
17. (英) T-Lymphocytes, Cytotoxic
18. (英) Thymoma
19. (英) Thymus Neoplasms

1. (英) Article.Affiliation: Department of Immunology and Parasitology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't