Experimental Hepatology, Inflammation and Cancer

Tumors consist of cancer cells and a multitude of other cell types that, through complex interactions, successfully create a tumor microenvironment (TME) that sustains cancer growth and assists in immune evasion. The recent success story of successful treatment by immune check point inhibitors in some cancer types illustrates the importance of anti-tumor immunity. However, the response rate on these therapeutics is very individual and dependent on the composition and activity of the cells in the TME. There is growing evidence that not only classic immunogenic factors, such as the mutational burden of cancer cells, define the anti-tumor immune response but that also oncogenic signaling pathways might play an important role in various ways through mechanisms not thoroughly understood yet.
Our lab investigates how different oncogenic signaling pathways each directly influence the TME and thus anti-tumor immunity. We focus primarily on liver cancer, which is characterized by a substantially genetic and morphologic heterogeneity and therefore particularly interesting to study. We use novel organoid-based preclinical liver cancer models that allow us to rebuild this genetic diversity and to study liver cancer in an immunologically intact setting. With single cell analyses we perform careful characterizations of the molecular cell-cell interactions and utilize functional genomic technologies to further probe their relevance. These models are complemented with organoid systems cultivated from human material.

The aim of our research is the classification of cancer genome – TME phenotype correlation patterns, the identification of immunotherapy resistance mechanisms specific to various oncogenic signaling pathways, and the discovery of therapeutically targetable pathway components of immune evasion, to formulate tumor-specific synergistic therapeutical approaches as a personalized treatment strategy.