Control of TCR-signalling specificity to combat liver cancer in the context of immunotherapy (P19)

在免疫治疗背景下控制 TCR 信号特异性来对抗肝癌 (P19)

• 批准号: 405445616
• 金额: --
• 依托单位: Institut für Malignom-, Metabolom- und Mikrobiomforschung (M3)
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405445616?language=en
• 关键词: Control; TCR; signalling; specificity; combat

Combinatorial immunotherapy of hepatocellular carcinoma has become the new standard of care. Although response rates and overall-survival improved - the benefit is relatively low. We have shown that fatty liver disease negatively affects immunotherapy due to aberrant TCR-signalling. We aim to reactivate cancer specific TCR-signalling to enable anti-cancer immunity in the context of fatty liver disease: Anti-PD1/anti-VEGFα treatment will be combined with drugs targeting lipid metabolism, oxidative stress or innate immune cells – to reprogram TCR-signalling and to alter the liver environment. Further, we aim to characterize the TCR-signalling repertoire on single-cell level and link to therapy response efficacy.

肝细胞癌的组合免疫治疗已成为新的治疗标准。尽管缓解率和总体生存率有所提高，但获益相对较低。我们已经证明，由于 TCR 信号异常，脂肪肝疾病会对免疫治疗产生负面影响。我们的目标是重新激活癌症特异性 TCR 信号传导，以在脂肪肝疾病的背景下实现抗癌免疫：抗 PD1/抗 VEGFα 治疗将与针对脂质代谢、氧化应激或先天免疫细胞的药物相结合，以重新编程 TCR 信号传导并改变肝脏环境。此外，我们的目标是在单细胞水平上表征 TCR 信号传导库，并将其与治疗反应功效联系起来。