Abstract

Monocytes/macrophages (MO/MA) represent a major leukocyte population in the peritoneal cavity of patients with epithelial ovarian cancer (EOC). We examined the phenotypic characteristics and antitumor cell activity of ascitic MO in patients with EOC. MO/MA phenotype was compared with MO in peripheral blood by two- and three-color flow cytometry. Cytotoxic/cytostatic effects of different cytokines on cultured EOC cells were measured by initial labeling or uptake inhibition of [methyl-³H] thymidine. Malignant ascites had higher proportion of MO/MA with the CD14^brightCD16⁺ phenotype than peripheral blood. Cell surface antigen expression of activation and differentiation in peripheral blood and ascites, including CD38, CD40, CD64, and CD86, was higher on CD14^brightCD16⁻ and CD14^brightCD16⁺ than on CD14^dimCD16⁻ cells. HLA-DR expression was higher on ascitic MO/MA than peripheral blood MO. Significant cytotoxic/cytostatic activity was elicited by treating ascitic MO/MA with interferon-γ (IFN-γ) and interleukin-2 (IL-2), but not with interleukin-12, paclitaxel, granulocyte-monocyte colony-stimulating factor (GM-CSF), or tumor necrosis factor-alpha (TNF-α). Soluble CD40Lt did not enhance MO/MA cytotoxic activity, and inhibited IFN-γ or IL-2 induced cytoxicity. We conclude that MO/MA from ascites have elevated proportions of CD14^brightCD16⁺ cells, showing phenotypic features of activation. IFN-γ induces the cytotoxic and cytostatic activity of MO/MA that is inhibited by CD40Lt.