Klinik für Innere Medizin IIGastroenterologie, Hepatologie, Endokrinologie und Infektiologie

Innate and adaptive immunity in viral hepatitis and hepatocellular carcinoma

T cell responses play an important role in the outcome of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus and hepatitis E virus (HEV) infection, e.g. viral elimination versus persistence. However, multiple mechanisms can lead to the failure of the virus-specific T cell response. These mechanisms include primary T cell failure, T cell exhaustion, the emergence of viral escape mutants, as well as T cell dysfunction. Furthermore, genetic factors such as the individual HLA allele background play an important role in the outcome of infection. Once viral persistence has been established, HBV or HCV infection can progress to liver fibrosis and cirrhosis with an enhanced risk for HCC. Tumor-specific T cells are thought to contribute to cancer control.

The focus of our group is the identification and characterization of virus-specific CD4+ and CD8+ T cell responses during acute and chronic HBV, HCV, HDV and HEV infection and the analysis of adaptive and innate immune responses against cancer. A specific focus is on the identification of the molecular determinants of T cell exhaustion and how this can be reversed in the setting of chronic viral infection and cancer. Indeed, in own previous work we could recently show that antigen-specific CD8+ T cells are heterogenous consisting of memory-like and terminally exhausted cells and that removal of antigen, for example by direct acting antiviral therapy leads to a disappearance of highly exhausted, but maintenance of a memory-like CD8+ T cell population. This memory-like population is characterized by specific phenotypical functional metabolic and transcriptional characteristics. On the CD4+ T cell level, we are interested in the lineage commitment of virus-specific CD4 helper T cells in different phases of viral hepatitis. Overall, these translational studies should give novel targets for immune therapy and help to identify biomarkers for prediction of response of different antiviral or immunotherapeutic therapies, such as checkpoint blockade. Another focus in our group is the analysis of innate immune responses in viral hepatitis and cancer with a specific focus on NK cells and gamma delta T cells. For example, we could recently show the expansion of adaptive/memory-like NK cells in chronic HBV virus infection. A further detailed understanding of the biological role of these innate subsets and their interaction with adaptive immune responses will be essential for the development of novel immunotherapeutic approaches.

Group of Maike Hofmann and Robert Thimme

Our studies are currently sponsored by:

• Sonderforschungsbereich-TRR179 (Deutsche Forschungsgemeinschaft, DFG)
• Sonderforschungsbereich 1160: IMPATH (Deutsche Forschungsgemeinschaft, DFG)
• Else Kröner-Fresenius-Stiftung: MOTI-VATE
• Europäische Union: Horizon 2020: HEP-CAR
• Deutsches Zentrum für Infektionsforschung DZIF (BMBF)

View all publications

• View all publications by Maike Hofmann in Pubmed
• View all publications by Robert Thimme in Pubmed