Project C03 (Augustin; HCC and the hepatic vascular niche: Analysis of angiocrine vascular targets) targets the tumor vasculature and has shown that the contextual agonistic and antagonistic Tie2 ligand Angiopoietin 2 (Angpt2) affects early stages of hepatocarcinogenesis but is dispensable in HCC progression, while the Tie2 coreceptor Tie1 affects HCC progression and metastasis. In the upcoming funding period project C03 will analyse the dynamic evolution of the vascular niche during HCC progression and metastasis using comprehensive scRNAseq-, proteome- and phospho-proteome data from LSEC in advanced genetically engineered mouse HCC models and a novel resectable electroporation-based HCC model. By this it will spatiotemporally deconvolute liver endothelial cell signatures during hepatocarcinogenesis. Tie1 will be pursued as a new therapeutic target alone and in combination with VEGFR- and immune checkpoint blockade. Furthermore, adoptive T-cell transfer experiments help to understand the tumor-immuno-endothelial crosstalk in controlling the tumor microenvironment for optimizing intervention strategies.
DFG Programme
CRC/Transregios
