NKT cell exacerbation of liver metastases arising from melanomas transplanted into either the eyes or spleens of mice

Wanhua Yang, Haochuan Li, Elizabeth Mayhew, Jessamee Mellon, Peter W. Chen, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

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Abstract

PURPOSE. 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.

Original languageEnglish (US)
Pages (from-to)3094-3102
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number6
DOIs
StatePublished - May 2011

Fingerprint

Natural Killer T-Cells
Melanoma
Spleen
Neoplasm Metastasis
Liver
Natural Killer Cells
Interleukin-10
Vitreous Body
Experimental Melanomas
Transforming Growth Factors
Inbred C57BL Mouse
Capsules
Immune Sera
Hepatocytes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

NKT cell exacerbation of liver metastases arising from melanomas transplanted into either the eyes or spleens of mice. / Yang, Wanhua; Li, Haochuan; Mayhew, Elizabeth; Mellon, Jessamee; Chen, Peter W.; Niederkorn, Jerry Y.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 6, 05.2011, p. 3094-3102.

Research output: Contribution to journalArticle

Yang, Wanhua ; Li, Haochuan ; Mayhew, Elizabeth ; Mellon, Jessamee ; Chen, Peter W. ; Niederkorn, Jerry Y. / NKT cell exacerbation of liver metastases arising from melanomas transplanted into either the eyes or spleens of mice. In: Investigative Ophthalmology and Visual Science. 2011 ; Vol. 52, No. 6. pp. 3094-3102.
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abstract = "PURPOSE. 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.",
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T1 - NKT cell exacerbation of liver metastases arising from melanomas transplanted into either the eyes or spleens of mice

AU - Yang, Wanhua

AU - Li, Haochuan

AU - Mayhew, Elizabeth

AU - Mellon, Jessamee

AU - Chen, Peter W.

AU - Niederkorn, Jerry Y.

PY - 2011/5

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N2 - PURPOSE. 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.

AB - PURPOSE. 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.

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