The IL-6/SAA axis in the hepatic tumor immune niche

Liver tumours are among the most frequently occurring tumours worldwide and display the third highest mortality rate with limited therapeutic options. Furthermore, the liver is a common site for metastatic colonisation of primary tumours such as e.g. colon cancer or breast cancer. In various cancer types, half of the patients develop liver metastasis that worsens a patients prognosis and are very difficult to treat. Novel therapeutic strategies are therefore highly sought after. There is compelling evidence that interaction of immune cells of the liver and the tumour cells is decisive for disease progression. The liver rather presents an organ with dampened immune reactions that enables growth of tumour cells. Small proteins, such as cytokines strongly contribute to the communication between diverse cell types. There are indications that the cytokine interleukin 6 (IL- 6) plays an important role in the immune micro-environment and cancerous events of the liver. In the project The IL-6/SAA axis in the hepatic immune niche, we will investigate in more depth, how IL-6 and subsequent signals regulate immune cells of the liver and how this impacts growth of liver tumours and liver metastasis. To this end, we will make use of novel technologies to label and analyse tumour-associated immune cells and of a recently developed mouse model that specifically allows to switch on and off IL-6 signalling pathways. We will furthermore analyse surgically removed tissue from patients with liver metastasis in order to address the question, if enhanced activation of IL-6 signalling pathways promotes liver metastasis. We will experimentally address if precise inhibition of an IL-6 downstream signalling pathway represents a novel therapeutic strategy. With our project we hope to gain novel insights into molecular mechanisms underlying the generation of a tumour-permissive immune micro-environment in the liver, in order to develop novel therapeutic approaches for the treatment of liver tumours and liver metastasis.