Cytolytic and cytostatic activity on tumor cells of circulating human monocytes

Abstract

AbstractMonocytes from the peripheral blood of normal adult human donors were found to have appreciable levels of cytotoxic activity against murine and human tumor‐cell lines. Adherent cells ( > 90% monocytes) were obtained from the peripheral blood of 29 normal healthy volunteers either by adherence on plastic and scraping with a rubber policeman or by adherence on microexudate‐coated plastic and exposure to ethylene diamine tetra‐acetic acid. Cytolytic capacity was tested by incubating effector cells for 72 h with murine and human tumor cell lines prelabelled with tritiated thy‐midine. Cytostasis was evaluated by inhibition of [125I]iododeoxyuridine (125IdUrd) uptake. Tumor target cells employed were: a murine SV40‐trans‐formed kidney line (TU5), a murine chemically‐induced sarcoma (1023), a human breast‐cancer‐derived cell line (G11) and a human lung‐cancer‐derived cell line (CaLu). Monocyte preparations at attacker to target cell ratios of 1:1 to 40:1, showed significant cytolytic and cytostatic activity against tumor target cells. Tumor cells showed different susceptibility to cytolytic activity, whereas comparable levels of cytostasls were observed with the various targets: TU5 and G11 tumor cells were more susceptible than 1023 and CaLu target cells to the cytolytic capacity of human monocytes and TU5 was used in most subsequent experiments. Peak isotope release from prelabelled target cells was observed after 72 h of incubation, whereas peak inhibition of [125I]dUrd uptake occurred after 24 h of culture. The cytotoxic capacity of monocytes isolated by either of the two methods mentioned above was similar. The monocytes had higher cytotoxic activity than unseparated mononuclear cells, and non‐adherent cells showed minimal cytotoxic effects. Cytotoxicity by natural killer cells did not appear to have a major role in these assays, since adherent cells did not lyse K562 cells in a 4‐h 51Cr release assay. Treatment with anti‐human T‐cell serum and complement did not inhibit the cytotoxic capacity of the monocyte preparations, whereas exposure to silica particles significantly inhibited the cytotoxic activity. Monocyte‐mediated cytotoxicity on tumor cells was expressed in the presence of both fetal bovine serum and human AB serum.