2023 Fiscal Year Final Research Report
Activation of upper respiratory mucosal immune response by immune checkpoint inhibitors
| Project/Area Number |
20K09717
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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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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平野 隆 大分大学, 医学部, 講師 (20305056)
川野 利明 大分大学, 医学部, 講師 (30633424)
門脇 嘉宣 大分大学, 医学部, 助教 (10706980)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 上気道感染症 / インフルエンザ菌 / 粘膜免疫 / 加齢 / PD1経路 / PD-L1 |
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| Outline of Final Research Achievements |
Aged Mice (12- and 18-month-old mice) were used in this study, they were administered intranasally 10 μg of OMP and 1 μg of cholera toxin as mucosal adjuvant three times a week. Intranasal administration was combined with anti-PD-L1 antibody administration in order to activate mucosal immunity. On day 7 after intranasal immunization, nasal lavage fluid and serum were collected and OMP-specific antibody titers were measured. Nasal mucosa, nasal mucosa-associated lymphoid tissue , cervical lymph nodes, and spleen were collected, flow cytometric analysis was performed. OMP-specific antibody increased with anti-PD-L1 antibody administration in 12-month-old mice. However, 18-month-old mice showed no increase in OMP-specific antibody titer. Twelve-month-old mice showed an enhanced CD69 expression in CD4-positive T lymphocytes. In addition, follicular helper T cells showed an increasing trend in lymphoid tissues in 12-month-old mice, but not 18-month-old mice.
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| Free Research Field |
耳鼻咽喉科
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| Academic Significance and Societal Importance of the Research Achievements |
本邦における65歳以上の侵襲型インフルエンザ菌感染症の主な疾患は肺炎であり、次いで菌血症、髄膜炎であり、症例致死率少なくなく、インフルエンザ菌分離株の95％は無莢膜型であるとの報告があり、高齢者におけるインフルエンザ菌経鼻粘膜ワクチンによる上気道免疫応答の賦活化は重要である。抗PD-L1抗体投与によるインフルエンザ菌経鼻粘膜ワクチンに対する上気道免疫応答の再活性化は12カ月齢マウスのみであり、18カ月齢マウスにおいて効果を認めなかった。しかし、PD-1経路ブロックによる粘膜免疫応答の再活性化の可能性が示され、高齢者に対するインフルエンザ菌ワクチン療法の確立に寄与すると考えられる。
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