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

免疫相关不良事件(IrAE)限制了ICIS的使用。IrAEs是由ICI诱导的自身抗体(Ab)或自身反应性T细胞对自身组织的自身免疫引起的。我们在人类肺细胞中发现了由人类白细胞抗原A24呈递的GPRC5A衍生肽表位，目前正在研究自身反应性T细胞和/或抗GPRC5A抗体是否可能与ICIS患者肺组织的炎症和损伤有关。我们已经证实，A24-TG动物的肺组织表达人类白细胞抗原-A24，并且能够处理和呈递与人类细胞相同的GPRC5A衍生肽表位。

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.