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

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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.