Suppression or enhancement by superoxide dismutase of tumor cell killing by macrophages of normal donors and breast cancer patients

Abstract

This study was designed to examine the role superoxide production by macrophages plays in tumor killing. When superoxide dismutase was added to the normal macrophage-tumor cell (MA-160 cell line) suspensions macrophage mediated tumor cytotoxicity was suppressed. In contrast, superoxide dismutase often greatly enhances the cytotoxic ability of macrophages from breast cancer patients. To determine whether the inability of breast cancer patients' macrophages to kill tumor cells might be related to decreased levels of O2- production, we measured the amount of O2- generated by both normal and breast cancer patients' macrophages. The macrophages obtained from the normal donors produced 46.0 +/- 6.7 nanomoles O2-/10(6) macrophages per 10 minutes (mean +/- S.E. of 9 donors). In contrast, macrophages from the four breast cancer patients who possessed cytotoxic macrophages produced 56.4 +/- 5.2 nanomoles O2-/10(6) macrophages per 10 minutes whereas those from the 6 breast cancer patients who possessed non-cytotoxic macrophages produced 18.6 +/- 3.2 nanomoles O2-/10(6) macrophages per 10 minutes. Thus, it appears that there is a relationship between macrophage cytotoxicity and the level of O2- produced. Furthermore, it is possible that the inability to generate sufficient amounts of O2- might explain the inability of breast cancer patients' macrophages to kill tumor cells in some cases.