Abstract EN:

Natural Killer (NK) cells are cytotoxic innate lymphoid cells discovered 45 years ago. Numerous studies have demonstrated their roles in the defense against pathogens and in the anti-tumor immune response. Consistent with their diversity of functions, NK cells are now recognized as a heterogeneous population. Yet, the recent discovery of type 1 innate lymphoid cells (ILC1) drastically increased the complexity of their study. ILC1 share numerous features with NK cells and until recently, the majority of NK cell studies targeted both populations. Here, we are revisiting some observations made about NK cells through this newly NK cell-ILC1 dichotomy. First, we examined their functions in a tumoral context. NK cells were discovered for their ability to kill tumor cells in vitro and in vivo. But, few studies addressed their role in the tumor immunosurveillance process. Using a chemical carcinogen-induced primary tumor model, we showed that NK cells and ILC1 do not play a critical role during the development of primary tumors. Nonetheless, this project allowed us to characterize their contribution in the elimination of transplantable tumors. Opposed to the anti-tumor role of NK cells, intratumoral ILC1 seem to have an inhibitory action on the anti-tumor immune response. In parallel, we also studied the development of liver-resident ILC1. NK cells and ILC1 belong to two distinct cell lineages but their developmental trajectories remain largely unknown. We discovered that liver ILC1 are generated from tissue-resident progenitors distinct from bone marrow-derived hematopoietic stem cells. We also showed that this process relies of the production of IFN-γ by the ILC1 themselves.