Elucidation of genomic alteration after boron neutron capture therapy in salivary gland carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K16867
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Chiba University (2020-2022); Tokyo Women's Medical University (2018-2019)
• Principal Investigator: Fukumoto Ichiro 千葉大学, 医学部附属病院, 助教 (70748764)
• Project Period (FY): 2018-04-01 – 2023-03-31
• 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

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.

Free Research Field

癌ゲノム

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。