title: Innate Response to Human Cancer Cells with or without IL-2 Receptor Common γ-Chain Function in NOD Background Mice Lacking Adaptive Immunity.
abstract: Immunodeficient hosts exhibit high acceptance of xenogeneic or neoplastic cells mainly due to lack of adaptive immunity, although it still remains to be elucidated how innate response affects the engraftment. IL-2R common γ-chain (IL-2Rγc) signaling is required for development of NK cells and a subset of dendritic cells producing IFN-γ. To better understand innate response in the absence of adaptive immunity, we examined amounts of metastatic foci in the livers after intrasplenic transfer of human colon cancer HCT116 cells into NOD/SCID versus NOD/SCID/IL-2Rγc (null) (NOG) hosts. The intravital microscopic imaging of livers in the hosts depleted of NK cells and/or macrophages revealed that IL-2Rγc function critically contributes to elimination of cancer cells without the need for NK cells and macrophages. In the absence of IL-2Rγc, macrophages play a role in the defense against tumors despite the NOD Sirpa allele, which allows human CD47 to bind to the encoded signal regulatory protein α to inhibit macrophage phagocytosis of human cells. Analogous experiments using human pancreas cancer MIA PaCa-2 cells provided findings roughly similar to those from the experiments using HCT116 cells except for lack of suppression of metastases by macrophages in NOG hosts. Administration of mouse IFN-γ to NOG hosts appeared to partially compensate lack of IL-2Rγc-dependent elimination of transferred HCT116 cells. These results provide insights into the nature of innate response in the absence of adaptive immunity, aiding in developing tumor xenograft models in experimental oncology.
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan; Central Institute for Experimental Animals, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan;
authors.forename: Chiyoko
authors.initials: C
authors.lastname: Nishime
authors.affiliation: Central Institute for Experimental Animals, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan;
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan;
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Central Institute for Experimental Animals, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan;
authors.forename: Ikumi
authors.initials: I
authors.lastname: Katano
authors.affiliation: Central Institute for Experimental Animals, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan;
authors.forename: Makoto
authors.initials: M
authors.lastname: Monnai
authors.affiliation: Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, Shinjuku-ku, Tokyo 162-8480, Japan;
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Goda
authors.affiliation: Central Institute for Experimental Animals, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan;
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Central Institute for Experimental Animals, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suemizu
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Shimokasuya, Isehara, Kanagawa 259-1193, Japan;
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan; and.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan; Japan Science and Technology Agency, Exploratory Research for Advanced Technology Suematsu Gas Biology Project, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan; and wakuism@a6.keio.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Wakui
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D059447:Cell Cycle Checkpoints; D004195:Disease Models, Animal; D045325:HCT116 Cells; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000008:administration & dosage; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000235:genetics*
chemical_list: D053631:Interleukin Receptor Common gamma Subunit; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma