April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Liver NKT cells enhance, rather than inhibit, liver metastases arising from intraocular melanomas in mice
Author Affiliations & Notes
  • Jerry Y Niederkorn
    Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX
  • Leila Sadegh
    Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX
  • Peter w Chen
    Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX
  • Joseph R Brown
    Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX
  • Footnotes
    Commercial Relationships Jerry Niederkorn, None; Leila Sadegh, None; Peter Chen, None; Joseph Brown, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4063. doi:
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      Jerry Y Niederkorn, Leila Sadegh, Peter w Chen, Joseph R Brown; Liver NKT cells enhance, rather than inhibit, liver metastases arising from intraocular melanomas in mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4063.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To determine the role of natural killer (NK) T cells in the development of liver metastases arising from intraocular melanomas in mice and the effect of NKT cells on NK cell activity in the livers and spleens of mice with hepatic metastases.

Methods: B16LS9 melanoma cells were transplanted either into the posterior compartment of the eye or into the portal vein of wild-type (WT) mice, NKT cell-deficient mice (CD1d knockout [KO]) mice or WT mice treated with anti-CD1d antibody. In other experiments melanoma cells were transplanted into IL-10 KO mice. IL-10 receptor expression on liver NK cells was assessed by qPCR and flow cytometry. NK cytolytic activity against melanoma cells was assessed in vitro.

Results: The absence of liver NKT cells mitigated, rather than exacerbated, the development of melanoma metastases in the liver and also significantly (P<0.01) enhanced the cytolytic activity of liver NK cells, but not NK cells in the spleen. IL-10 expression was elevated in the livers of WT mice compared to NKT cell-deficient mice. NK cells taken from the livers of WT mice had significantly higher expression of IL-10R compared to their counterparts in NKT cell-deficient mice. The NK cell activation receptor, NKG2D, was significantly (P<0.01) higher on liver NK cells in NKT cell-deficient mice compared to WT mice.

Conclusions: Although employing NK-based immunotherapy for various malignancies is an attractive propositon, our results suggest that such therapies need to take into consideration the cross regulatory effect of NKT cells on NK cells and that the location of the NK cells has a profound effect in determining if NK cell activity is suppressed or activated and whether metastatic disease is mitigated or exacerbated.

Keywords: 553 immune tolerance/privilege • 555 immunomodulation/immunoregulation • 589 melanoma  
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