Expression of ζ in T Cells Prior to Interleukin-2 Therapy as a Predictor of Response and Survival in Patients with Ovarian Carcinoma

Abstract

Expression levels of T-cell receptor (TcR)-associated ζ chain were reported to reflect functional competence of T lymphocytes in patients with cancer. This retrospective study was performed to evaluateζ chain expression in circulating T cells obtained from clinical responders and nonresponders among 19 patients with advanced ovarian carcinoma treated with intraperitoneal interleukin-2 (IL-2) biotherapy. Banked lymphocytes, which were collected from the patients who participated in a phase I clinical trial performed between 1987 and 1990, were used for quantitative flow cytometry to measure ζ-chain expression in T lymphocytes prior to and at the end of therapy. The data were correlated with 7-year survival. The patients (9 responders and 10 nonresponders) were stratified into two groups based on ζ chain expression in CD3+ T cells above or below the mean. Patients with lower ζ expression in circulating T cells had shorter survival compared to patients whose T cells expressed high ζ. Pretherapyζ expression was significantly lower (p = 0.03) in CD8+ T cells of nonresponders than in CD8+ T cells of normal controls. In patients with advanced ovarian carcinoma, low expression of the ζ chain in peripheral blood T cells prior to biotherapy might both reflect a large tumor burden and predict a poor of response to IL-2 biotherapy.