Zebrafish as a novel organism model to study immunogenic cell death-related mechanisms

Immunogenic cell death (ICD) is a cell death modality induced by specific clinically used anticancer therapeutics, which is able to stimulate anti-tumor immunity. It can result in an anticancer vaccination effect during treatment. All knowledge existing so far on ICD and immunosurveillance has been generated in mice models. However, the use of mice is accompanied with prolonged times for the establishment/growth of neoplastic lesions and significant expenses. These particular conditions slow down dramatically new developments and new insights in the field. Besides, methodologies relying on rodent-related work are also intrinsically unsuited to the concept of HTS (High-Throughput Screening) necessary to find novel and safe ICD-inducers. In recent years, the zebrafish has proven to be a unique vertebrate model for the study of organ development, function and many human diseases. Zebrafish is biologically remarkably similar to humans, as 70% of protein-coding human genes are related to genes found in zebrafish and 82% of genes known to be associated with human diseases have a zebrafish counterpart. In this project we will establish zebrafish as a novel organism model for ICD and anticancer immunity analysis. We will use a liver cancer model that can be induced in zebrafish to dynamically study broad consensus immunosurveillance mechanisms during tumor development which may provide crucial information for the further optimization of anticancer vaccination strategies.