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

肝癌的联合免疫治疗已成为新的治疗标准。虽然反应率和总体生存率有所提高，但获益相对较低。我们已经表明，由于异常的tcr信号传导，脂肪肝疾病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，从而在脂肪肝疾病的背景下实现抗癌免疫：抗pd1 /抗vegf α治疗将与靶向脂质代谢、氧化应激或先天免疫细胞的药物联合使用，以重新编程tcr信号并改变肝脏环境。此外，我们的目标是在单细胞水平上表征tcr信号传导库，并将其与治疗反应疗效联系起来。

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.