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

肝细胞癌的联合免疫治疗已成为新的治疗标准。尽管应答率和总体存活率有所改善，但受益相对较低。我们已经证明，由于TCR信号的异常，脂肪肝对免疫治疗产生了负面影响。我们的目标是重新激活癌症特异性TcR信号，以在脂肪肝的背景下实现抗癌免疫：抗PD1/抗血管内皮生长因子α治疗将与针对脂代谢、氧化应激或先天性免疫细胞的药物相结合-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信号转导系统，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.