Maturation of dendritic cells from ovarian cancer patients

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 f rom the ascites of patients with ovarian or peritoneal carcinoma, have the cell surface characteristics of immature cells. Moreover, p70 interleukin-1 2 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 f rom peripheral blood and ascites samples of patients with ovarian cancer wi th either cytokines or proteolytic enzymes (polyenzyme preparation). Method s: Mononuclear leukocytes from the ascites of 15 patients or peripheral blo od 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 alpha 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 m ixed leukocyte reaction (MLR) and higher concentrations of IL-12 were detec ted after growing these cells in the presence of cytokines or enzymes as co mpared to tissue culture medium alone. Conclusion: Our studies demonstrate for the first time that DC obtained from the peritoneal cavity and peripher al blood of ovarian cancer patients after culturing in the presence of a po lyenzyme preparation, will undergo maturation. Further studies are warrante d to determine whether polyenzyme preparations facilitate DC maturation in vivo.