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Uncovering the mechanisms of inflammation induced liver tissue destruction and carcinogenesis

Final Report Summary - LIVERCANCERMECHANISM (Uncovering the mechanisms of inflammation induced liver tissue destruction and carcinogenesis)

In our ERC Starting grant (Liver Cancer Mechanism) we have investigated the role of inflammation on liver cancer development. By establishing several different mouse model fully recapitulating human patholgoy we could identify which immune cells contribute to inflammation induced cancer in the liver.

We could show that immune cells not only drive the carcinogenic development of hepatocytes per se - but we could also demonstrate that immune cells generate a microniche - we defined these inflammatory structures as ectopic lymphoid structures (ELSs) (mainly composed of lymphocytes) which also function as a nutrition niche for cancer cells to develop.

Besides, we could show that other inflammatory structures - mainly composed of myeloid cells - are beneficial in the context of boosting an inflammatory response that can be beneficial for infections and - at the long run - also for cancer development in the liver. These structures are called iMATEs for intrahepatic myeloid aggregates of T cell expansion.

Moreover, we could also demonstrate that viral proteins themselves can drive liver cancer (e.g. the Hepatitis Antigen HBsAg) and that under conditions of liver inflammation but high HBsAG blocking of inflammatory signalling (eg. NFKb signalling) actually increases liver cancer and thereby is harmful.

Finally, we could show that particular inflammatory signalling cascades (e.g. the lymphotoxin beta recetpor signaling cascade) can be used to eradicate Hepatitis B Virus infections in a non cytotoxic manner.