Inhibition of Pulmonary Metastasis by Intravenous Injection of Specifically Activated Macrophages

The ability of syngeneic macrophages from C57BL/6 mice bearing a progressively growing B16 melanoma to inhibit established pulmonary metastases in vivo was studied. Macrophages were cultured in vitro with supernatants obtained from cultures of B16 tumor cells alone or tumor cells and either normal, nonspecifically sensitized or specifically sensitized xenogeneic (rat) lymphocytes. The different groups of in vitro-treated macrophages were injected i.v. or i.p. into other C57BL/6 mice that had been given i.v. injections of 10, 000 viable B16 melanoma cells 48 hr previously. The data demonstrated that specifically in vitro-treated macrophages injected i.v. but not i.p. into mice significantly reduced their number of established pulmonary metastases. Moreover, it appeared that the in vivo inhibition of tumor nodules was continuing at the time of sacrifice. These results support the experimental data that cytotoxic macrophages may occupy an important role in the defense against neoplasia. Furthermore, the application of xenogeneic activation of macrophages from tumor-bearing animals rendering them cytotoxic may provide a possible approach to therapy.