Identification of regulators of cancer: immune interactions

Abstract

Despite the interest and success in immunotherapy, our current understanding of how the immune activation balance – on the macro level – and the expression of receptors and their ligands – on the micro level – shape health and disease is still limited. By identifying novel regulatory networks that dictate immune cell activity in physiologically relevant settings, well-designed pooled genetic screens could offer a relevant approach to address this knowledge gap. Genetic screens have become a powerful tool to identify

genes that affect the response and phenotype of a cell in an unbiased manner.In this thesis, I aimed to identify regulators of immune cell activation in the context of cancer through a combination of in vitro and in vivo genetic screens and genetically modified mouse models. Specifically, this was achieved by both 1) using genetic screening technologies to identify novel cancer cell-expressed inhibitory ligands or regulators

of immune-modulating ligands in an unbiased manner, and 2) investigating the effect of these regulators on the cellular components and signaling pathways that constitute the local tumor microenvironment and potentially dictate anti-tumor efficacy.