Depletion of NK cell activity results in growth of hepatic micrometastases in a murine ocular melanoma model

Abstract

PURPOSE. To study the role of natural killer (NK) cells in growth of spontaneous hepatic metastasis in a murine intraocular melanoma model. METHODS. Tissue culture B16-LS9 melanoma cells were analyzed by flow cytometry for MHC class I expression of all haplotypes and inoculated into the posterior compartment (PC) of one eye of C57BL6 mice. The eyes were enucleated at 12 days post-inoculation and histologically examined for tumor growth. One group of mice (n = 10) were given intraperitoneal injections of anti-asialo GM1 for NK cell depletion post-enucleation and a second group of mice (n = 9) served as controls. The mice were sacrificed at 24 days post-inoculation and necropsies were performed to determine the number and size of metastasis. RESULTS. The B16-LS9 cells failed to express MHC class I antigen. Tumor grew in the PC of all eyes and metastasized to the lungs and livers of all mice, with the average number of hepatic micrometastases greater in the NK depleted group versus the control group (p =. 009). There was no significant difference in the average number of pulmonary metastases in the treated versus the control group (p =. 072). Hepatic metastases grew to an average diameter of 600 µm in diameter in two NK depleted mice. CONCLUSIONS. NK depletion in this model of metastatic ocular melanoma results in increased number and growth of hepatic micrometastases.