Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Abstract

Malignant tumors may contribute to host response that involves both the adaptive and innate immune systems. Among other biochemical indicators of systemic immune and inflammatory activity, activation of macrophages by interferon-gamma induces a marked increase in the production of neopterin. Neopterin production by activated macrophages is also associated with tryptophan degradation. In addition to tumors of other primary locations, increased urinary and serum neopterin concentrations have been reported in patients with gynecological cancers, including epithelial ovarian carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign neoplasms or precancerous disorders. Increased neopterin concentrations have been associated with poor prognosis. Elevated levels of neopterin have also been observed in the tumor microenvironment. Systemic (urinary or serum) or local (ascitic fluid) neopterin concentrations increased after therapeutic administration of cytokines. Elevated neopterin concentrations have been associated with anemia of chronic disease and increased urinary zinc loss in patients with gynecological malignancy. Elevated neopterin has also been connected with depressed function of peripheral blood lymphocytes and a decrease in CD4+ T-cell numbers.

Systemic Immune Activation, Anemia and Thrombocytosis in Breast Cancer Patients Treated by Doxorubicin and Paclitaxel

“…because neopterin production is the result of activation by IFN-γ, systemic immune activation. An increase in serum or urinary ncopterin concentrations in cancer patients has been amply documented (7,8). High neopterin concentrations have been observed in patients with tumor presenting mostly in advanced stage, e.g.…”

Serum Neopterin in Patients with Malignant Melanoma

“…An increase in serum or urinary neopterin concentrations in cancer patients has been amply documented (15,16), but less is known about neopterin in patients with melanoma. Neopterin determination has been used to monitor systemic effects of cytokine therapy in melanoma patients.…”

“…Increased neopterin concentrations are thought to reflect immune dysregulation. In patients with tumors of different primary locations, increased serum or urinary neopterin concentrations were associated with poor prognosis (15,16). The number of patients in the present study and short follow up did not allow us to investigate the prognostic significance of serum neopterin concentrations.…”

Neoadjuvant combination therapy with trastuzumab in a breast cancer patient with synchronous rectal carcinoma: a case report and biomarker study

“…Increased urinary neopterin concentrations were reported in <20% of breast cancer patients [40,46]. Neopterin concentrations correlated with tumor grade and the presence of advanced disease [40,46], and increased neopterin was indicative of poor prognosis in both univariate and multivariate analyses [46].…”

“…Neopterin concentrations are therefore thought to reflect both systemic immune and inflammatory responses [32]. Serum or urinary neopterin can be used as a biomarker of systemic immune and inflammatory responses in a wide range of disorders including malignancies, viral infections, transplant rejection, advanced age or atherosclerosis and its complications [32][33][34][35][36][37][38][39][40]. Neopterin is stable in refrigerated samples for up to 2 weeks, and samples for repeat assessment may be collected and stored by the patient between regular office visits with the need for repeated puncture circumvented.…”