Innate lymphoid cells have emerged as a potent innate immune cell population with key roles in homeostasis, as well as in forming first line of defense against infections. Increasing evidences also highlight their involvement in different pathologies such as inflammatory diseases and cancers. Extensive work is being performed by us and others to unravel ILC biology and their underlying mechanisms of actions, both in physiology and in diseases.

In this work, we were able to decipher the complex transcriptomic and epigenetic regulation of human peripheral ILCs. We exposed and identified a high inter-subsets complexity, with each core ILC subset (i.e., ILC1s, ILC2s, ILCPs) further divided in subclusters, showing a high level of heterogeneity and providing a resource database for future studies in patients. In addition, we uncovered the underlying mechanisms leading to ILC2 pro-tumoral phenotype in bladder cancer, highlighting for the first time the role of a neurotrophic factor, NGF, regulating ILC2 functions in the context of tumor immunity.