Ability of cancer patients' macrophages to kill autologous tumor targets. Effect of prostaglandin inhibitors on cytotoxicity.
Monocyte-derived macrophages isolated from the peripheral blood of 17 patients with cancer were studied for their cytotoxic effects on a sensitive allogeneic tumor target as well as autologous tumor cells. Macrophages from four of the cancer patients were cytotoxic towards the allogeneic tumor target. Five patients had macrophages which were cytotoxic towards the autologous targets. When indomethacin, a prostaglandin inhibitor, was added to the noncytotoxic macrophages during the cytotoxicity assay, macrophages from 5 of the 11 cancer patients studied became cytotoxic for the allogeneic target, and macrophages from 4 of the 11 patients became cytotoxic for the autologous tumor cells. However, it was also noted that those cancer patients who possessed cytotoxic macrophaged in the absence of indomethacin, became noncytotoxic towards the tumor cells after addition of indomethacin. These results indicate that addition of indomethacin to cytotoxic macrophages suppresses macrophage mediated cytotoxicity whereas addition of indomethacin to noncytotoxic macrophages greatly enhances macrophage mediated cytotoxicity. This theory was further substantiated when it was observed that the cytotoxic macrophages obtained from normal donors also became noncytotoxic for a sensitive tumor cell line after the addition of indomethacin during the cytotoxicity assay.
D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D011448:Prostaglandin Antagonists
D011448:Prostaglandin Antagonists; D007213:Indomethacin