Tumoricidal activity of macrophages isolated from human ascitic and solid ovarian carcinomas: augmentation by interferon, lymphokines and endotoxin

Abstract

Peripheral blood monocytes and macrophages from ascitic or solid tumors were obtained from 50 patients with advanced (Stage III or IV) ovarian carcinoma. Blood monocytes and peritoneal macrophages from 76 patients undergoing surgery for benign gynecological diseases were used as controls. Macrophages were 30% (range 0.2-6.2) and 2% (range 0.2-4) of mononuclear cell suspensions from ascitic and solid tumors, respectively. Cytolytic activity was measured as release of [3H]-thymidine from prelabelled mKSARU5 (TU5) target cells at an effector to target cell ratio of 20:1. Peripheral blood monocytes and tumor-associated macrophages had baseline cytotoxicity lower than or similar to that of control peripheral blood and peritoneal macrophages respectively. In vitro exposure to partially purified human fibroblast interferon, lymphokine supernatants or endotoxin augmented the cytotoxicity of mononuclear phagocytes, and no significant difference was observed between control and ovarian cancer effector cells from peritoneal effusions. In four patients, macrophages were isolated from the solid tumor or from the malignant effusion and tested in parallel: in two out of four subjects, macrophages from the solid neoplasm showed defective cytotoxicity compared to ascites effector cells from the same subject. When primary ovarian carcinoma cultures were used as targets, tumor cells from two out of five patients tested were relatively resistant to activated macrophage cytotoxicity. Thus, tumor-associated macrophages from ascitic or solid ovarian neoplasms showed no evidence of activation, in terms of spontaneous cytotoxicity or responsiveness to stimuli: it appears unlikely that small numbers of non-activated macrophages present within primary ovarian carcinomas act as a significant mechanism of restraint of neoplastic growth, at least at this anatomical site.