Differential effects of an immunosuppressive fraction from ascites fluid of patients with ovarian cancer on spontaneous and antibody-dependent cytotoxicity

Abstract

The ascites fluids from humans with cancer that has metastasized to the peritoneum is suppressive of the immune response both in vitro and in vivo. The active moiety is present in a high-molecular-weight fraction which elutes in the void volume of a Sephadex G-200 column. This fraction (designated Peak I) has been shown to inhibit a number of in vitro responses and will inhibit the antibody response to sheep red blood cells in vivo. In this report, the Peak I protein fraction from the ascites of patients with ovarian cancer is shown to inhibit spontaneous cytotoxicity of human mononuclear cells against the myeloid cell line K562 and against the T-lymphoid cell line Molt-4F. This fraction was active at concentrations of 1 to 3 mg/ml. In contrast to this finding, it was not possible to demonstrate an inhibition of antibody-dependent cell cytotoxicity against chicken red blood cells. Preincubation of the effector cells with Peak I prior to addition to the chicken red blood cell targets or modification of the antibody concentration in the assay did not result in suppression; in fact, in many experiments, the Peak I potentiated cytotoxicity against chicken red blood cells. The Peak I proteins were also tested in an antibody-dependent cell cytotoxicity assay against a transformed cell line (HeLa cells), and there was no significant suppression of cytotoxicity. Peak I protein fractions prepared as controls from normal human serum and a congestive heart failure fluid were not suppressive, whereas the Peak I fraction from a cirrhotic fluid was suppressive of natural killing activity.