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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 CD14brightCD16+ 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 CD14brightCD16- and CD14brightCD16+ than on CD14dimCD16- 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-gamma (IFN-gamma) and interleukin-2 (IL-2), but not with interleukin-12, paclitaxel, granulocyte-monocyte colony-stimulating factor (GM-CSF), or tumor necrosis factor-alpha (TNF-alpha). Soluble CD40Lt did not enhance MO/MA cytotoxic activity, and inhibited IFN-gamma or IL-2 induced cytoxicity. We conclude that MO/MA from ascites have elevated proportions of CD14brightCD16+ cells, showing phenotypic features of activation. IFN-gamma induces the cytotoxic and cytostatic activity of MO/MA that is inhibited by CD40Lt.

Increased urinary concentrations of neoptcrin, an indicator of systemic immune activation, have been reported only in a minority of patients with breast cancer. We determined urinary neopterin by high-performance liquid chromatography in 78 patients with breast carcinoma, including 51 patients treated by systemic administration of doxorubicin and paclitaxel. Urinary neopterin before the therapy was not statistically different in patients compared to controls. Increased neopterin concentrations were more frequent in patients with advanced disease. A statistically significant increase in urinary neopterin, gradual decrease in hemoglobin and an increase in platelet counts were observed during doxorubicin/paclitaxel chemotherapy. The concentration of urinary neopterin before the second cycle of chemotherapy has shown significant negative correlation with the concentrations of hemoglobin later in the course of chemotherapy and a positive corrélation with platelet counts. In conclusion, urinary neopterin is normal in most patients with breast cancer. Increased urinary neopterin concentrations during doxorubicin/paclitaxel chemotherapy indicate the presence of systemic immune activation that seems to be associated with chemotherapy-induced anemia and thrombocytosis.

In previous studies, mostly in patients with early stage colorectal carcinoma, neopterin, an indicator of systemic immune activation, has been associated with poor prognosis. The aim of the present study was to evaluate urinary neopterin in patients with advanced or metastatic colorectal carcinoma treated with chemotherapy. A retrospective analysis was performed of urinary neopterin, determined by high-performance liquid chromatography, in 88 patients with advanced or metastatic colorectal carcinoma. Peripheral blood cell count and serum carcinoembryonic antigen (CEA) were determined in 72 patients before the start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was significantly increased compared to controls, but lower than in patients with inflammatory bowel disease. Neopterin correlated significantly with serum CEA, age, peripheral blood leukocyte and platelet counts. The median survival of colorectal carcinoma patients with urinary neopterin below 214 micromol/mol creatinine was significantly longer compared to that of patients with higher neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and hemoglobin were also associated with survival in univariate analysis, but in multivariate analysis only urinary neopterin and serum CEA were independent predictors of survival. High urinary neopterin during follow-up was also predictive of poor prognosis.

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