Abigail Spaulding

A novel focus in cancer immunotherapy is the utilization of γδ T-cells (gamma delta T-cells), a subset of immune cells that do not require neoantigen expression to attack cancer cells. Instead, γδ T-cells attack metabolically dysregulated cancer cells by recognition of butyrophilin (BTN) proteins expressed on the cell surface. Activating the γδ T-cells to attack cancer cells involves both excessive accumulation of mevalonate pathway intermediates and “stressing” the cancer cells, specifically through a reduction energy levels and subsequential activation of AMP-activated protein kinase (AMPK). ErSO family compounds (BHPI, ErSO, ErSO-DFP and ErSO-TFPy), discovered by the Shapiro and Hergenrother lab, cause necrotic cell death in cancer cells by inducing lethal hyperactivation of the normally tumor protective stress response pathway, the anticipatory unfolded protein response (aUPR). These compounds significantly deplete cellular ATP, inducing strong activation of AMPK. My study will determine if activation of AMPK by the ErSO family compounds can elicit an increase of γδ T cell activation and killing of cancer cells.