Kurzfassung

Innate lymphoid cells (ILCs) are newly discovered innate cells which can be classified into two main branches, cytotoxic ILCs (NK cells) and helper-like ILCs (ILC1, 2, 3). ILCs are located at mucosal barriers and play an important role during infections, but their impact on cancer is poorly understood. It has been suggested that ILC3s have an immunosuppressive effect on the tumor microenvironment, possibly due to their interaction with epithelial and stromal cells. In contrast, potent...Innate lymphoid cells (ILCs) are newly discovered innate cells which can be classified into two main branches, cytotoxic ILCs (NK cells) and helper-like ILCs (ILC1, 2, 3). ILCs are located at mucosal barriers and play an important role during infections, but their impact on cancer is poorly understood. It has been suggested that ILC3s have an immunosuppressive effect on the tumor microenvironment, possibly due to their interaction with epithelial and stromal cells. In contrast, potent anti-tumor activity has been assigned to the NKp46+ subset of ILC3s in IL-12-producing tumors suggesting that different ILC subsets could differentially affect tumor progression. Importantly, the molecular mechanisms involved in anti- or pro-tumoral activities of ILC3s are entirely unknown. We hypothesize that the molecular machinery generating ILC3 plasticity could be targeted to manipulate the tumor microenvironment and to restrict tumor progression. To this aim, we will define the spatiotemporal distribution of ILC populations within solid tumors and we will characterize them, with particular attention to ILC3 plasticity and functions. We will determine the impact of the different ILC3 subsets on cancer progression by using different mouse lines lacking specific ILC3 subsets. We will perform an extensive analysis of lymphoid and myeloid tumor-infiltrating cells and their pro- or anti-tumoral activities, in order to evaluate immunoregulatory functions of the various ILC3 subsets. The knowledge of the role of the different ILC3 subsets on cancer progression will allow the development of clinical approaches to target “bad” and to harness the power of the “good” ILC populations. The main ILC feature is the orchestration of the environment by behaving as helper-like cells. Therefore, the exploitation of their plasticity could represent an important new tool to “re-program” the tumor microenvironment with the aim to unleash efficient immunity against cancer.
 
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