Natural killer cell migration in pregnancy and immunosurveillance regulated by PI3K

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A class of white blood cells specialised in sensing cancer cells and destroyomg them, known as natural killer cells, are generally found in the circulation and in blood vessels of various organs, including lymph glands, bone marrow, liver and lungs. Surprisingly, these killer cells specifically expand in the uterus during pregnancy, supplying growth factors that help to build up the placenta that feeds the growing fetus. How do these fascinating cells achieve such different functions? One deciding factor is the microenvironment they travel to, which provides cues for these cells to develop into killers or builders. We have found that the molecular switch PI3K guides killer cells in their circulation. When this molecular switch is inactivated by genetic or pharmacological means, killer cells do not traffic normally to tumours and to the uterus. Our research plan, structured in three sections, aims to: i) understand how PI3K regulates the transition of killer cells from within the blood into the tissue; (ii) explore the mechanisms of killer cell migration to the site of tumour growth and metastasis; iii) appreciate how PI3K contributes to the placenta-building function of killer cells and its consequences on healthy fetal growth.