Targeting the pro-oncogenic ER-stress mediator ATF6 to reset the immunosuppressive tissue-microenvironment in liver cancer

Project Summary

Activating Transcription Factor 6 alpha (ATF6) has pro-oncogenic/immunosppressive function in the liver. In a model of chronic inflammation-induced liver cancer, the PIs were able to show that the specific knock-out of ATF6 in hepatocytes abrogates liver cancer formation. P10 will use transgenic mice that express or lack nuclear ATF6 specifically in hepatocytes (nATF6liv) to understand how local increase of active ATF6 affects the immune system in HCC. In addition the connection between ATF6 and immune cell infiltrates in HCC will be investigated. To use this information therapeutically, P10 will target ATF6 and treat HCC with ICB to identify a synergism.