Abstract
Natural killer (NK) cells are innate immune cells that are critical to the body’s antitumor and antimetastatic defense. As such, novel therapies are being developed to utilize NK cells as part of a next generation of immunotherapies to treat patients with metastatic disease. Therefore, it is essential for us to examine how metastatic cancer cells and NK cells interact with each other throughout the metastatic cascade. In this Review, we highlight the recent body of work that has begun to answer these questions. We explore how the unique biology of cancer cells at each stage of metastasis alters fundamental NK cell biology, including how cancer cells can evade immunosurveillance and co-opt NK cells into cells that promote metastasis. We also discuss the translational potential of this knowledge.
Highlights
Natural killer (NK) cells are lymphoid members of the innate immune system that have potent antitumor and anti-metastatic abilities [2, 3]. Since their identification in the 1970s, natural killer (NK) cells have been described as critical contributors to the immune control of cancer cells [4–15]
While the cytotoxic activity of NK cells has long been linked to anti-metastatic activity and the reduction of distant site metastases [73], recent studies have focused on the function of NK cells and their interactions at specific stages of metastasis
As cancer cells began to proliferate into macrometastases, these NK cell activating signals were reversed. These findings suggest that the kinetics and specific functional properties of metastatic cancer cells dictate their sensitivity to NK cell–mediated immunoediting (Figure 1)
Summary
Natural killer (NK) cells are innate immune cells that are critical to the body’s antitumor and antimetastatic defense.
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