The role of oncogene-driven activation of the CMTM6 / PD-L1 axis in leukaemia immune escape (P03)

癌基因驱动的CMTM6/PD-L1轴激活在白血病免疫逃逸中的作用（P03）

• 批准号: 464624579
• 金额: --
• 依托单位: Klinik für Innere Medizin I - Hämatologie, Onkologie und Stammzelltransplantation
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/464624579?language=en
• 关键词: role; oncogene; driven; activation; CMTM6

P03 aims to identify oncogenic drivers of the protein CMTM6 – a stabilizer of PD-L1 surface expression – in leukaemia cells. Preliminary data show a link between oncogenic signalling, CMTM6 and PD-L1 in AML cells. P03 will decipher the downstream signalling events that promote CMTM6 and PD L1 expression in leukaemia cells. The effect of CMTM6 deficiency in leukaemia cells on T cell activation, metabolism and exhaustion and leukaemia immune escape will be studied in vitro and in immunocompetent murine AML models. P03 will clarify how oncogenic upregulation of the CMTM6/PD L1 axis contributes to leukaemia immune escape and whether CMTM6 blockade/deletion can enhance anti-leukaemia immune responses.

P03旨在识别白血病细胞中蛋白质CMTM 6（PD-L1表面表达的稳定剂）的致癌驱动因素。初步数据显示AML细胞中致癌信号传导、CMTM 6和PD-L1之间存在联系。P03将破译促进白血病细胞中CMTM 6和PD L1表达的下游信号传导事件。将在体外和免疫活性小鼠AML模型中研究白血病细胞中CMTM 6缺陷对T细胞活化、代谢和耗竭以及白血病免疫逃逸的影响。P03将阐明CMTM 6/PD L1轴的致癌上调如何促进白血病免疫逃逸，以及CMTM 6阻断/缺失是否可以增强抗白血病免疫应答。