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

• Subject Area: Hematology, Oncology ; Immunology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 360372040

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.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1335: Aberrant Immune Signals in Cancer
• Applicant Institution: Technische Universität München (TUM)
• Project Head: Professor Dr. Mathias Heikenwälder