Understanding the spatio-temporal changes of the metastatic lymph node epicenter

Lymph nodes (LN) are the first metastatic relay before cancer disseminate to distant organs. There is growing evidence that tumor-emanating signals create a premetastatic niche in sentinel LN that facilitate metastatic cell dissemination. However, the mechanistic underpinnings of how tumor cells induce a pre-metastatic niche in LNs and escape cell death and immunosurveillance upon seeding in the LN are less understood. The PhD project aims to generate and use optically barcoded cancer cell lines to resolve the dynamics and behavior of single cancer cells during the distinct lymph node metastasis stages. The project will involve in vitro cell- and organoid culture, the use of in house engineered mouse models, advanced 3D- and intravital imaging, multiplex immunohistochemistry, and single cell analyses & cell lineage studies. The candidate will study mechanisms of cancer cells dissemination in the LN, and perform characterization of cancer cell states, their metabolic rewiring and crosstalk with LN resident immune cells and endothelial cells. A specific focus will be on how cellular states or LN neighborhoods confer resistance to cell death. Used technologies are cellular barcoding, in house generated mouse models, advanced intravital microscopy, and single-cell sequencing.