Interactions entre effecteurs lymphocytaires et cellules leucémiques

Natural Killers (NK) cells are innate lymphoid cells with a strong cytotoxicity and cytokine production potential in the context of cancer, especially hematological malignancies. Acute Myeloid Leukemia (AML) is a disorder consisting of the expansion of myeloid cells blocked in an immature stage of myelopoiesis. Both in humans and mice, NK cells present phenotypic, functional and transcriptional alterations in AML. Overall these cells acquire a phenotype of activated cells but reshaped towards non-cytotoxic features. We have demonstrated that these cells have a defective IL-15 signaling, which may be due to exhaustion by chronic but ineffective stimulation. We observed that NK cells are found nearby developing leukemia foci in the BM at early stages of leukemia development in mice. The aim of the project is to analyze the profile of NK cells surrounding leukemia cells, to verify whether and which other immune cells are also present, and to identify the mechanisms allowing this “recruitment “and whether it is linked to the acquisition of immune defects. The study will require flow cytometry, confocal microscopy and in vitro assays.