Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis

Significance Innate lymphoid cells hold great promise for the treatment of metastases. Development of effective therapies based on these versatile immune cells, however, is hampered by our limited knowledge of their behavior in the metastatic niche. Here, we describe that defense against liver metastasis requires collaboration between two innate lymphocyte subsets, conventional NK cells (cNKs) and tissue-resident type I innate lymphoid cells (trILC1s). We show that different cancers generate their own particular metastatic niche–inducing specific changes in cNKs and trILC1s. Furthermore, we uncover specific cNK subsets that can be manipulated to improve their antimetastatic potential. Our work contributes to understanding how cancer-specific factors and hepatic innate lymphocytes exert mutual influence and how this can be exploited for therapeutic purposes.