Innate response to human cancer cells with or without IL-2 receptor common γ-chain function in NOD background mice lacking adaptive immunity

Chiyoko Nishime, Kenji Kawai, Takehiro Yamamoto, Ikumi Katano, Makoto Monnai, Nobuhito Goda, Tomoko Mizushima, Hiroshi Suemizu, Masato Nakamura, Mitsuru Murata, Makoto Suematsu, Masatoshi Wakui

Research output: Contribution to journalArticle

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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-2Rgc) 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-2Rgc null (NOG) hosts. The intravital microscopic imaging of livers in the hosts depleted of NK cells and/or macrophages revealed that IL-2Rgc function critically contributes to elimination of cancer cells without the need for NK cells and macrophages. In the absence of IL-2Rgc, 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 a 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-2Rgc-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.

Original languageEnglish
Pages (from-to)1883-1890
Number of pages8
JournalJournal of Immunology
Volume195
Issue number4
DOIs
Publication statusPublished - 2015 Aug 15

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Inbred NOD Mouse
Interleukin-2 Receptors
Adaptive Immunity
HCT116 Cells
Macrophages
Natural Killer Cells
Neoplasms
Cytophagocytosis
Liver
Pancreatic Neoplasms
Heterografts
Colonic Neoplasms
Dendritic Cells
Theoretical Models
Alleles
Neoplasm Metastasis
Proteins

ASJC Scopus subject areas

  • Immunology

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Innate response to human cancer cells with or without IL-2 receptor common γ-chain function in NOD background mice lacking adaptive immunity. / Nishime, Chiyoko; Kawai, Kenji; Yamamoto, Takehiro; Katano, Ikumi; Monnai, Makoto; Goda, Nobuhito; Mizushima, Tomoko; Suemizu, Hiroshi; Nakamura, Masato; Murata, Mitsuru; Suematsu, Makoto; Wakui, Masatoshi.

In: Journal of Immunology, Vol. 195, No. 4, 15.08.2015, p. 1883-1890.

Research output: Contribution to journalArticle

Nishime, Chiyoko ; Kawai, Kenji ; Yamamoto, Takehiro ; Katano, Ikumi ; Monnai, Makoto ; Goda, Nobuhito ; Mizushima, Tomoko ; Suemizu, Hiroshi ; Nakamura, Masato ; Murata, Mitsuru ; Suematsu, Makoto ; Wakui, Masatoshi. / Innate response to human cancer cells with or without IL-2 receptor common γ-chain function in NOD background mice lacking adaptive immunity. In: Journal of Immunology. 2015 ; Vol. 195, No. 4. pp. 1883-1890.
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