Regulation of the metastasis of murine ocular melanoma by natural killer cells

In the current study we examine parameters affecting the metastasis of ocular tumors of in vivo derived B16F10 melanoma. In C57BL/6J beige (bg/bg) mice, with low NK activity, metastasis to the lungs was increased and survival time decreased. In C57BL/6J normal (+/+) mice treatment with PK136, a highly specific monoclonal anti-NK antibody (Ab), caused a depletion of NK cytotoxic activity, as demonstrated using a standard 51Cr release assay. In animals bearing ocular tumors, treatment with PK136 Ab resulted in significantly increased pulmonary metastasis and an altered pattern of metastasis. The effect of combined treatment protocols using LS2616 (linomide) and cyclophosphamide (Cy) was examined in enucleated and unenucleated animals. Treatment with LS2616 and Cy resulted in a significant decrease in mean pulmonary metastases (MPM), a decreased frequency of metastasis to the submandibular lymph nodes and an increase in mean survival time. In enucleated mice this combined treatment protocol resulted in apparent cures, the lowest MPM and the longest survival time observed. When tumor-bearing mice were treated with either silica, carrageenan or sublethal gamma irradiation, no effect on metastasis or survival was observed. This study demonstrates the importance of the NK cell as a primary effector cell for the control of metastasis from in vivo derived ocular B16F10 melanoma.