Cytotoxicity to tumor cells of monocytes from normal individuals and cancer patients

Abstract

This study was aimed at characterizing the parameters which regulate human monocyte-mediated cytotoxicity to tumor cells as well as characterizing the target cell specificity, kinetics, etc., of the cytotoxic mechanism. Normal human peripheral blood monocytes were cytotoxic to tumor cells in an in vitro assay, measuring release of [³H]thymidine from human target cells. Monocyte cytolysis was observed with several adherent tumor lines including T24, a bladder cancer line; LR, a melanoma line; and an SV40-transformed W138 fibroblast line, with maximal cytolysis observed at 72 h. Lymphokines were not required to induce and only infrequently enhanced monocyte cytotoxicity. Prolonged exposure of monocytes to lymphokines or in vitro culturing of monocytes prior to lymphokine exposure did not alter the monocytes' response to lymphokine signals with respect to cytotoxicity. Lymphokines induced monocytes to exhibit enhanced spreading, suggesting that monocytes were susceptible to lymphokine signals but that the development of cytolytic function was independent of lymphokines. In contrast to the cytolysis of adherent tumor cells, monocytes were less effective in killing the non-adherent lymphoid target cells K562, Raji, and CEM. Monocytes were selectively cytotoxic to tumor cells and generally did not kill normal human fibroblast cell lines or PHA-stimulated lymphocytes. Monocytes from cancer patients exhibited normal cytotoxicity to several human tumor lines. Plasmas from some cancer patients were inhibitory to cytotoxicity mediated by both autologous monocytes and normal monocytes.