title: IFN-γ production by lung NK cells is critical for the natural resistance to pulmonary metastasis of B16 melanoma in mice.
abstract: 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.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan. ktakeda@juntendo.ac.jp
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Masashi
authors.initials: M
authors.lastname: Sakaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Michio
authors.initials: M
authors.lastname: Imawari
authors.forename: Kouetsu
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D045744:Cell Line, Tumor; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009928:Organ Specificity
chemical_list: D007371:Interferon-gamma