Giovanni Ledoux

Project: Exploring How Cancer Cell Motility Influences Trogocytosis Lethality

Lab Group: Morrissey Lab

Graduate Mentor: Annie Rogers

Abstract: Solid cancer tumors are countered by the body’s immune system through macrophages, an innate immune cell capable of whole cell engulfment (phagocytosis) or cellular nibbling (trogocytosis). Current cancer immunotherapies rely on engineered macrophages, CAR macrophages or antibody-dependent macrophages, to drive out assumed phagocytosed cancer cell-macrophage interactions. We have determined only 10% of interactions are phagocytosis, while 90% are trogocytosis; trogocytosis does not typically kill the cell and instead strips the antigen off the surface of cancer cells, creating cells resistant to therapies. Why trogocytosis is typically not lethal remains unclear. We hypothesize certain genes protect cancer cells from trogocytosis-mediated death. Conducting a genome-wide CRISPRi screen in ovarian cancer cells, we identified genes linked to motility and actin cytoskeleton dynamics that influence cancer cell death following trogocytosis. We hypothesize increased concentrations of actin cytoskeletal filaments along trogocytotic sites will be linked to preventing trogocytosis lethality. To explore how actin could be preventing trogocytosis lethality, we fluorescently labeled it and performed confocal microscopy to elucidate cancer cell actin dynamics during macrophage trogocytotic attack. Identifying the downstream behaviors and mechanisms will confirm its association with trogocytosis. Understanding this will provide novel insights into how target cell properties influence trogocytosis lethality and improve cancer immunotherapies.