Dissemination of tumor cells and metastasis represent the major cause of death in cancer patients. More than 5% of patients show liver metastases at the time of primary cancer diagnosis, a feature associated with poor prognosis and low 1-year survival rates. An increasing number of immunotherapies aim to target cancer cells by harnessing natural killer (NK) cells, taking advantage of their strong anti-tumor/anti-metastasis potential. NK cells belong to the family of innate lymphoid cells (ILC) and have the capacity to kill target cells directly. Very recently it has been shown that another population of ILCs, called ILC1, also possesses target cell-killing capacities. ILC1, in contrast to NK cells, do not recirculate in the body but reside in tissues and could represent a first line of defense against metastatic seeding. Currently, the understanding of the heterogeneity and function of NK cells and ILC populations that infiltrate metastases (MILCs) is limited, yet, knowledge thereof could be key for the development of optimized treatments. Therefore, the identification of novel cellular and molecular pathways underlying anti-metastatic activities of NK cells and ILC1 to inhibit tumor expansion and dissemination is a pressing unmet need.
In this research program, we aim at assessing the heterogeneity of NK cells and ILC1 in metastases from patients and different mouse models of metastasis to reveal type 1 effector programs that provide protection against metastatic spread that might serve to develop novel treatments.