The role of inflammation in the liver microenvironment of a Fibrolamellar Carcinoma zebrafish model

Dr. Sofia de Oliveira – Albert Einstein College of Medicine, New York, NY

Fibrolamellar Carcinoma (FLC) is a rare type of liver cancer that mainly affects children and young adults. The only genetic anomaly that has been associated with FLC is the DNAJB1-PRKACA fusion transcript (DnaJ-PKAc). Recently we have developed a FLC zebrafish model and reported that DnaJ-PKAc expression in hepatocytes triggers inflammation and induces inflammasome activation. There is a growing interest in potential contributions of innate immune cells on modulating tumorigenesis, which is leading to innovative strategies with the goal to elicit a more integrated immune response against cancer. Therefore, it is crucial to understand the role of innate immune cells in the liver microenvironment, and how they can modulate liver immune landscape. The zebrafish is the smallest and only vertebrate system that allows the visualization of the liver using non-invasive live imaging techniques, which makes our zebrafish FLC model an essential tool for studying the pathobiology of this malignancy. Here we propose to use our model to investigate how innate immune cells modulate liver microenvironment and immune landscape via inflammasome-mediated instruction in FLC. Our work will unravel immune mechanism involved on FLC biology, with the goal of developing effective immune therapies targeting FLC. In addition, our novel approach will expand our understanding about how innate immune cells are involved in the crosstalk and further instruction of adaptive immunity in the liver.