Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastases in vivo.

Effector lymphoid cells that inhibit hematogenous tumor metastasis in normal unimmunized mice were studied. Mice pretreated with cyclophosphamide (Cy) exhibited a diminished ability to destroy circulating tumor cells, which, in turn, caused an increased incidence of experimental pulmonary metastasis. Adoptive transfer of spleen cells from unimmunized syngeneic donors abrogated the Cy-induced enhancement of metastasis formation. The effector cell active in these adoptive transfer experiments was sensitive to treatment with specific anti-NK-1.2 antibodies and complement. This treatment was shown by in vitro tests to deplete or inactivate NK cells selectively. These findings provide direct evidence that NK cells play a significant role in the inhibition of hematogenous tumor metastases in vivo.