がん免疫療法における免疫関連有害事象発症のメカニズム解明

阐明癌症免疫治疗中免疫相关不良事件的机制

• 批准号: 21K08152
• 负责人: コーチン ビタリー
• 金额: $ 2.58万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K08152/
• 关键词: GPRC5A; irAEs,; ICIs; autoimmune Ab; cytotoxic T cells; irAEs; Autoimmune antibody; Cytotoxic T cells; Lung-related irAEs; Immune checkpoint

Immune Related Adverse Events (irAEs) restrain ICIs use. The irAEs are caused by ICI-induced autoimmunity against self-tissues by auto-antibody (Ab) or self-reacting T cells. We found GPRC5A-derived peptide epitope presented by HLA-A24 specifically in human lung cells and currently investigating whether autoreactive T cells and/or Ab to GPRC5A may be responsible for the inflammation and damage in lung tissue of patients who underwent treatment with ICIs.We use HLA-A24 transgenic MHC-KO mice (A24-Tg mice) as a model. We have confirmed that the lung tissue of the A24-Tg animals express HLA-A24 and can process and present GPRC5A-derived peptide epitope identical to the one in human cells.

免疫相关的不良事件（IRAE）限制ICIS的使用。 IRAE是由ICI引起的自身免疫性对自身抗体（AB）或自我反应T细胞的自身影响引起的。我们发现，HLA-A24特别在人类肺细胞中提出的GPRC5A衍生的肽表位，目前研究了自身反应性T细胞和/或AB到GPRC5A是否可能导致ICIS治疗的患者的肺部炎症和损伤。我们已经证实，A24-TG动物的肺组织表达HLA-A24，并且可以处理并呈现GPRC5A衍生的肽表位与人类细胞中的肽相同。

项目成果

PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes

• DOI: 10.1016/j.celrep.2022.110331
• 发表时间: 2022-02-01
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Nagasaki, Joji;Inozume, Takashi;Togashi, Yosuke
• 通讯作者: Togashi, Yosuke