Fig. 4

The function of group 1 ILCs in experimental liver metastases in mice. NK cells depend on IL-15 for their activation and exhibit immunosurveillance and cytotoxicity that allow them to actively drive antitumor functions. Although NK cells can eliminate tumor cells to control potential tumor metastasis, they can become dysfunctional within the cytokine milieu of the tumor microenvironment, which results in reduced killing of abnormal cells compared with naïve NK cells. In contrast to NK cells, ILC1s do not appear to readily infiltrate metastatic tumors to directly eliminate them but can control metastatic seeding by producing granzyme B and IFN-γ. The fact that they do not penetrate within the tumor spatially positions them distant from the immunosuppressive environment of the tumor, allowing them to retain their antimetastatic functions. Their development and antitumor functions rely on their expression of the transcription factor RORα. A recently described intermediate ILC1/NK cell type, CD49a⁺CD49b⁺Eomes⁺ cells, are present within nodules and produce high levels of granzyme B [94]. Although their role in tumors has not yet been fully elucidated, mice deficient in TGF-β signaling fail to develop CD49a⁺CD49b⁺Eomes⁺ cells and present with fewer metastases, suggesting a protumor function of these cells despite their high production of granzyme B