Harnessing NK Cells to Control Metastasis

In recent years, tumor immunotherapy has produced remarkable results in tumor treatment. Nevertheless, its effects are severely limited in patients with low or absent pre-existing T cell immunity. Accordingly, metastasis remains the major cause of tumor-associated death. On the other hand, natural killer (NK) cells have the unique ability to recognize and rapidly act against tumor cells and surveil tumor cell dissemination. The role of NK cells in metastasis prevention is undisputable as an increase in the number of these cells mostly leads to a favorable prognosis. Hence, it is reasonable to consider that successful metastasis involves evasion of NK-cell-mediated immunosurveillance. Therefore, harnessing NK cells to control metastasis is promising. Circulating tumor cells (CTCs) are the seeds for distant metastasis, and the number of CTCs detected in the blood of patients with tumor is associated with a worse prognosis, whereas NK cells can eliminate highly motile CTCs especially in the blood. Here, we review the role of NK cells during metastasis, particularly the specific interactions of NK cells with CTCs, which may provide essential clues on how to harness the power of NK cells against tumor metastasis. As a result, a new way to prevent or treat metastatic tumor may be developed.