Inhibition of lymphocyte mitogenesis by factor(s) released from macrophages isolated from ascitic fluid of advanced ovarian cancer patients

Summary

Ascitic fluid from women with advanced ovarian carcinomas was shown to contain factor(s) which inhibit(s) T lymphocyte mitogenesis. The factor(s) was (were) demonstrated to be associated with the infiltrating macrophages. The inhibition was reversible and inhibited mitogenesis at some late event in the cell cycle. The inhibitory substance(s) was (were) noncytotoxic, dialyzable, heat-stable at 70° C for 10 min (but unstable at 100° C for 15 min), and partially resistant to protease treatment (55%–70%). Further experiments demonstrated that macrophages isolated from the ascitic fluid of patients with cirrhosis of the liver also released factor(s) which inhibit(s) T lymphocyte mitogenesis. On the basis of our data and data from other investigators, we propose that in advanced human ovarian cancer of epithelial origin, macrophages which infiltrate the ascitic fluid elaborate nonspecific inhibitors of T lymphocyte blastogenesis within the proximal environment, resulting in localized immunosuppression and the subsequent enhancement of metastasis within the peritoneal cavity, the tumor cells themselves being resistant to the cytocidal action of the macrophages due to genetic selection and/or their inherent biochemical ability to circumvent normal immunosurveillance mechanisms. This may account, at least in part, for the rapid metastasis and poor prognosis of human ovarian adenocarcinomas.