title: NKT cell exacerbation of liver metastases arising from melanomas transplanted into either the eyes or spleens of mice.
abstract: OBJECTIVE
  To explore the role of natural killer T (NKT) cells in the development of liver metastases in mice harboring intraocular melanomas.
  
  
  METHODS
  Cells derived from the cutaneous B16 melanoma cell line (B16LS9) were transplanted either into the vitreous body or under the spleen capsules of wild-type C57BL/6 mice and NKT-cell-deficient Jα18(-/-) and CD1d(-/-) mice. The development of liver metastases was evaluated by histopathology. The effect of NK cells on liver metastases was determined by selective depletion with anti-asialo-GM1 antiserum in vivo and NK-cell-mediated cytolysis of B16LS9 melanoma cells in vitro. The role of IL-10 and transforming growth factor (TGF)-β in the inhibition of liver NK resistance to liver metastases was determined by in vivo and in vitro neutralization with monoclonal antibodies.
  
  
  RESULTS
  Liver NKT cells, especially type I NKT cells, enhanced liver metastases arising from intraocular melanomas. NKT-cell-deficient mice developed significantly fewer liver metastases that were NK-cell dependent. Tumor-induced liver NKT cells, especially type I NKT cells, inhibited liver NK-cell cytotoxicity by an IL-10-dependent process.
  
  
  CONCLUSIONS
  NKT cells exert protective effects in many murine tumor models. However, the present results reveal that NKT cells exacerbate liver metastases arising from intraocular melanomas. To the authors' knowledge, this is the first report that liver NKT cells, especially type I NKT cells, inhibit liver NK-cell antimetastatic activity by the production of IL-10. These results suggest that hepatic NKT cell activity can have an important effect in the immune surveillance of liver metastases.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9057, USA.
authors.forename: Wanhua
authors.initials: W
authors.lastname: Yang
authors.forename: Haochuan
authors.initials: H
authors.lastname: Li
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mayhew
authors.forename: Jessamee
authors.initials: J
authors.lastname: Mellon
authors.forename: Peter W
authors.initials: PW
authors.lastname: Chen
authors.forename: Jerry Y
authors.initials: JY
authors.lastname: Niederkorn
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005134:Eye Neoplasms / Q000276:immunology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005677:G(M1) Ganglioside / Q000276:immunology; D016753:Interleukin-10 / Q000502:physiology; D008099:Liver / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D009368:Neoplasm Transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013156:Splenectomy; D013160:Splenic Neoplasms / Q000276:immunology / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D014822:Vitreous Body / Q000276:immunology / Q000473:pathology*
chemical_list: D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside