Maturation of dendritic cells from ovarian cancer patients

Abstract.

Purpose: Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system. We have shown that DC, defined as LN^–DR⁺ leukocytes from the ascites of patients with ovarian or peritoneal carcinoma, have the cell surface characteristics of immature cells. Moreover, p70 interleukin-12 has not been detected in the ascites of ovarian cancer patients in vivo. In the current study, we examined the effects of in vitro treatment of DC from peripheral blood and ascites samples of patients with ovarian cancer with either cytokines or proteolytic enzymes (polyenzyme preparation). Methods: Mononuclear leukocytes from the ascites of 15 patients or peripheral blood from 9 patients with epithelial ovarian cancer were cultured with tissue culture medium containing either papain, trypsin and chymotrypsin for 5–7 days or recombinant human granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α and interleukin-4 (complete medium) or tissue culture medium alone. Results: Phenotypic analysis of DC obtained on days 5–7 of the culture showed higher proportions of CD83⁺, CD40⁺ and CD80⁺ cells when cultured with cytokines or enzymes as compared with DC cultured with medium alone. Stimulation of allogeneic T cells was detected by the mixed leukocyte reaction (MLR) and higher concentrations of IL-12 were detected after growing these cells in the presence of cytokines or enzymes as compared to tissue culture medium alone. Conclusion: Our studies demonstrate for the first time that DC obtained from the peritoneal cavity and peripheral blood of ovarian cancer patients after culturing in the presence of a polyenzyme preparation, will undergo maturation. Further studies are warranted to determine whether polyenzyme preparations facilitate DC maturation in vivo.