title: The innate immune receptor Dectin-2 mediates the phagocytosis of cancer cells by Kupffer cells for the suppression of liver metastasis.
abstract: Tumor metastasis is the cause of most cancer deaths. Although metastases can form in multiple end organs, the liver is recognized as a highly permissive organ. Nevertheless, there is evidence for immune cell-mediated mechanisms that function to suppress liver metastasis by certain tumors, although the underlying mechanisms for the suppression of metastasis remain elusive. Here, we show that Dectin-2, a C-type lectin receptor (CLR) family of innate receptors, is critical for the suppression of liver metastasis of cancer cells. We provide evidence that Dectin-2 functions in resident macrophages in the liver, known as Kupffer cells, to mediate the uptake and clearance of cancer cells. Interestingly, Kupffer cells are selectively endowed with Dectin-2-dependent phagocytotic activity, with neither bone marrow-derived macrophages nor alveolar macrophages showing this potential. Concordantly, subcutaneous primary tumor growth and lung metastasis are not affected by the absence of Dectin-2. In addition, macrophage C-type lectin, a CLR known to be complex with Dectin-2, also contributes to the suppression of liver metastasis. Collectively, these results highlight the hitherto poorly understood mechanism of Kupffer cell-mediated control of metastasis that is mediated by the CLR innate receptor family, with implications for the development of anticancer therapy targeting CLRs.
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan.|Japan Research and Open Innovation, Sanofi K.K., Tokyo 163-1488, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan.|Max Planck-The University of Tokyo Center for Integrative Inflammology, Tokyo 153-8505, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Hangai
authors.affiliation: Department of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Negishi
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nishio
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan.|Max Planck-The University of Tokyo Center for Integrative Inflammology, Tokyo 153-8505, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yanai
authors.affiliation: Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan; tada@m.u-tokyo.ac.jp.|Max Planck-The University of Tokyo Center for Integrative Inflammology, Tokyo 153-8505, Japan.
authors.forename: Tadatsugu
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007728:Kupffer Cells / Q000502:physiology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000556:secondary*; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology*; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: C584161:Clec4d protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; C445340:dectin-2, mouse
keywords: C-type lectin receptor; Dectin-2; Kupffer cell; liver metastasis; phagocytosis