| Project/Area Number |
18K16867
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | Chiba University (2020-2022)
Tokyo Women's Medical University (2018-2019) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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)
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| Keywords | 唾液腺癌 / 腺様嚢胞癌 / 免疫チェックポイント阻害薬 / ホウ素中性子捕捉療法 / 腫瘍免疫 / 耳下腺癌 / 耳下腺腺様嚢胞癌 / 癌遺伝子 |
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| Outline of Final Research Achievements |
Exhaustive analysis was performed on samples before and after BNCT in adenoid cystic carcinoma patients following surgical resection. Using the data from RNA sequencing, differentially regulated genes and pathways were identified.
Expressions of genes involved in the anti-tumor immune response was enriched in post-BNCT samples. Particularly, gene expressions on T cells (CD2, CD3ε) and surface molecules involved in T cell activity regulation (CLAT-4, ICOS) were elevated after BNCT. Furthermore, the TCR signaling pathway was upregulated upon BNCT. The enrichment of T cell markers suggested immune cell recruitment after BNCT. Elevated CTLA-4 and ICOS expressions raise the possibility that the modulation of these receptors’ activities via immune checkpoint inhibitors or agonistic monoclonal antibodies may be an effective combination strategy with BNCT.
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| Academic Significance and Societal Importance of the Research Achievements |
唾液腺腺様嚢胞癌は外科手術が第一選択だが、遠隔転移をきたした症例は化学療法や放射線療法が中心の治療になる。現在分子標的薬を含めた化学療法や放 射線療法が検討されているが、有効な治療法が確立されてないのが現状である。ホウ素中性子捕捉療法(Boron Neutron Capture Therapy: BNCT)はその中でも効果が期待できる新たな治療だが、BNCTに対して治療抵抗性を示す腺様嚢胞癌では腫瘍免疫学的な機序が関与している可能性が示唆され、今後新たな治療法が期待できると考えられた。
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