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H. E. Grossniklaus, H. Yang, P. Liu; Interferon 2b Control of Hepatic Metastases in Murine Ocular Melanoma Model Is Dependent on Interferon , Perforin and TNF. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1503.
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© ARVO (1962-2015); The Authors (2016-present)
Our laboratory has previously shown that interferon α2b (IFNα2b) decreases the number of hepatic micrometastases in a murine ocular melanoma model. The purpose of this study is to further define the immunologic mechanisms of this action of IFNα2b.
C57Bl/6 mice were inoculated into the posterior compartment of the right eye with equal aliquots of B16LS9 melanoma cells. Four strains of mice were utilized: wild type and the followng knockouts: interferon γ (IFNγ), perforin and tumor necrosis factor α (TNFα) (Jackson labs). The mice were treated with 10,000 international units (IU) IM IFNα2b or an equal volume of PBS for four days prior to enucleation, and the right eye was enucleated 7 days after inoculation. The mice were sacrificed at 21 days post-enucleation (28 days post-inoculation). Grossly visible metastases (>1mm) diameter and microscopically identified hepatic metastases (>10µm diameter) and micrometastases (≤ 10 µm) were enumerated. Survival was determined as percent alive at four weeks after enucleation.
There was a significant difference in metastatic rate between IFNα2b treated wild type and control mice (p=0.7X10-5). There were significant metastatic rate differences between IFNγ (p=0.04), perforin (p=0.02) and TNFα (p=0.05) mice vs wild type. There were also significantly different metastatic rates between IFNα2b treated IFNγ (p=0.01), perforin (p=0.04) and TNFα (p=0.002) mice vs PBS treated mice. All PBS treated mice had metastases surrounded by micrometastases whereas all IFNα2b treated mice only had micrometastases. The incidence of grossly visible hepatic metastases ranged from 0% (wild type) to 60% (INFγ PBS treated group). Survival ranged from 80% (wild type IFNα2b treated group) to 20% (INFγ PBS treated group).
Intrinsic immunologic control of murine ocular melanoma hepatic metastasis is INFγ, perforin and TNFα dependent. Exogenously administered IFNα2b augments this control via NKT cell mediated melanoma lysis (INFγ, perforin) and FAS mediated (TNFα) pathways.
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