Project A04 (Heikenwälder/Claassen; Platelet aggregation and activity in steatosis-HCC) has shown that activated platelets drive NASH-induced hepatocarcinogenesis by initiating inflammation through interaction with Kupffer cells, sinusoidal endothelial cells and hepatocytes mainly via the mediator GPIbα. Thus, inhibition of the proinflammatory and carcinogenic function of platelets by blocking the GPIbα ectodomain reversed NASH and NASH-driven hepatocarcinogenesis. In the next funding period this surprising e mechanism will be further specified by identifying the relevant platelet subsets through a multi-omics approach using mouse NASH-HCC models and patient probes. Next, the effect of liver vasculature ‘normalisation’ and immune checkpoint blockade on platelet numbers and functions in HCC will be determined. Machine learning models (Claassen) will reveal correlations and potential causalities of platelet (de-)activation for response to immune checkpoint inhibition and antiangiogenic treatment.
DFG Programme
CRC/Transregios
