Project Description

Understanding how the immune system affects cancer progression remains one of the fundamental questions in cancer biology and is crucial for the development of effective therapies. To dissect the molecular mechanisms of immune evasion and their emergence during tumour dormancy and metastatic colonization, we will use established metastasis models combined with a novel technique we have developed, utilizing CRISPRa to trace clones in heterogeneous cell populations (CaTCH; Umkehrer et al. submitted). CaTCH enables lineage tracing of millions of cells with stably integrated DNA barcodes (BCs). Importantly, activation of a reporter allows FACS-based isolation of clones with distinct phenotypes of interest (i.e. tumour cells that stay dormant or escape dormancy in an immune-competent or -deficient background), enabling their mechanistic workup. We will assess the immune-contexture, mutational load and the transcriptional programs in the selected cancer cell clones and their pre-selection counterparts. By integrating clinical data, we will identify candidate mediators of these phenotypes, probe their role in functional metastasis assays (gain/loss of function) and dissect the underlying mechanisms.