NK cells are effector lymphocytes playing a critical role in the natural resistance against tumors. However, the precise mechanisms underlying NK cell-mediated natural resistance against tumor metastasis are still unrevealed. B16 cells, mouse melanoma cells, were resistant to freshly isolated NK cell-mediated killing; nevertheless, NK cells were critical for natural resistance against experimental lung metastasis of B16 cells. We found that lung metastasis was increased significantly in IFN -γ -/- mice but not pfp -/-, IFN -αR -/-, or IL-12/IL-18 -/- mice. Interestingly, freshly isolated lung NK cells, but not spleen or liver NK cells, displayed augmented IFN -γ production after B16 inoculation. Adoptive transfer of pfp -/- NK cells, but not IFN -γ -/- NK cells, significantly decreased B16 lung metastasis in IFN -γ -/- and pfp/IFN -γ -/- mice. Lung metastases of IFN -γRDN B16 was also increased in NK cell-depleted or IFN -γ -/- mice, suggesting that the IFN -γ response of host cells was required in the NK cell and IFN -γ-mediated antimetastatic effect. Our results demonstrate that IFN -γ production from lung resident NK cells is a key response in the natural resistance to the experimental lung metastasis of NK cell-resistant tumor cells.
- Cytotoxicity · microenvironment · embolization