Thursday, March 4, 2021 -
12:00 to 13:00

BMC Seminar Thursday 4 March, 12:00

Speaker: Hildur Knútsdóttir, PhD, Postdoctoral Fellow in Joel S. Bader‘s lab, Institute for Computational Medicine, Johns Hopkins University, USA

Title: Characterizing cancer-specific invasion programs and deciphering the role of natural killer cells in metastatic breast cancer

Abstract: Metastasis is responsible for 90% of cancer-related deaths. Despite its clear importance, we have an incomplete understanding of the molecular requirements for metastatic spread. Furthermore, tumors are heterogenous entities composed of several clones expressing different molecular programs leading to both inter- and intra-tumor heterogeneity. In this talk, I will explain how we exploit this heterogeneity in 3D organoid models of invasion to identify novel drivers of metastasis. Next, we used organoid co-culture models to study the role of natural killer (NK) cells in tumor surveillance. We discovered that exposure to breast cancer cells causes NK cells to lose their cytotoxic ability and promote metastatic outgrowth. Gene expression comparisons revealed that healthy NK (hNK) cells have an active NK cell molecular phenotype while tumor-exposed NK (teNK) cells resemble resting NK cells. Receptor-ligand analysis between teNK cells and tumor cells revealed multiple potential therapeutic targets which were verified experimentally.  Our data suggest that NK directed therapies could be used in the adjuvant setting to treat and prevent the outgrowth of metastatic disease.

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