| Project/Area Number |
17K10533
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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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| Research Field |
General surgery
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Iguchi Akiko 筑波大学, 医学医療系, 講師 (50575644)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | TIGIT / DNAM-1 / CD155 / 免疫チェックポイント分子 / TIL / 乳癌 / 腫瘍免疫 / 癌 / 免疫学 |
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| Outline of Final Research Achievements |
To analyze the expression of the novel immune checkpoint molecule TIGIT, the paired receptor DNAM-1 and the ligand CD155, immunostaining of TNBC and HER2 positive breast cancer tissue was performed for CD155 / PD-L1 in breast cancer cells and normal ductal epithelial cells, in addition, CD4 / CD8 / CD68 / Poxp3 / TIGIT in TIL. Both TNBC and HER2 positive breast cancer showed more TIL in the tumor part than in the normal part, and more expression of CD8, CD68, and Foxp3. Moreover, the expression of CD155 in breast cancer cells and the expression of TIGIT in TIL were observed. Expression of DNAM-1 in TIL has not been confirmed, and analysis will continue. Furthermore, we succeeded in establishing a soluble CD155 knock-in mouse, and are currently analyzing the interaction of each molecule in carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
TIGITは免疫チェックポイント分子として新しく見出された分子で、T細胞やNK細胞に発現する抑制性受容体であり、リガンドのCD155を同じくT細胞やNK細胞に発現する活性型受容体DNAM-1と共有する。CD155は膜型のほかに可溶型のアイソフォームを持ち、膜型、可溶型ともTIGIT、DNAM-1と結合することから、可溶型CD155が膜型CD155とTIGITあるいはDNAM-1との相互作用を阻害する可能性などが考えられる。癌組織におけるこれらの分子の発現局在を明らかにするこの研究は、これらの分子の複雑な相互作用を解明する一助になると言える。
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