In vitro effects on tumor cells of macrophages isolated from an early-passage chemically-induced murine sarcoma and from its spontaneous metastases

Abstract

Macrophages were isolated by adherence from an early-passage chemically-induced tumor in C57BL/6 mice and from its spontaneous lung metastases. Cytolytic activity was measured as release of [3H]-thymidine from prelabelled tumor cells and cytostasis in a postlabelling assay. Normal, unstimulated peritoneal macrophages exhibited low but significant non-specific cytotoxic activity at attacker to target (A:T) ratios greater than or equal to 20:1, whereas stimulation of tumor-cell proliferative capacity was consistently observed at A:T ratios less than or equal to 2.1, Macrophages from the peritoneal cavity of tumor-bearing mice, from the primary tumor or from polled secondaries had baseline cytotoxic or growth-enhancing (depending on the A:T ratio) potential similar to that of control peritoneal macrophages. In vitro exposure to endotoxin, lymphokine supernatants or partially purified fibroblast interferon augmented the tumoricidal activity of normal and tumor-associated macrophages; tumor-associated macrophages showed no evidence of enhanced responsiveness to these activating stimuli. Tumor cells from the primary neoplasm and its spontaneous metastases were equally susceptible to macrophage tumoricidal activity. It is inferred from in vitro data that the relatively low numbers of non-activated macrophages present within poorly immunogenic metastasizing tumors may have no direct effect or actually stimulate tumor-cell proliferative capacity at the primary tumor site; conversely, disseminating tumor cells might encounter sufficient numbers of mononuclear phagocytes in the circulation and in lungs to permit the expression of macrophage cytotoxicity, at least during the early steps of metastasis formation.