Prognostic Significance of Circulating Cytotoxic Lymphocytes Against Autologous Tumors in Patients With Bladder Cancer

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Abstract
Cell-mediated immunity is an important and central mechanism of host resistance to cancer. Many studies have used cultured tumor cell lines as targets for cell-mediated cytotoxicity. However, it is difficult to interpret the data generated from the cytotoxic activity against cultured tumor cell lines, since they may not represent the activity against fresh autologous tumor cells. We examined the prognostic significance of circulating antitumorigenic cytotoxic lymphocytes at operation.Peripheral blood lymphocytes derived from 89 patients with a bladder tumor were tested at operation for cytotoxic activity against a natural killer sensitive myeloid leukemia line K562, a human bladder tumor cell line T24 and freshly isolated autologous tumor cells in a 12-hour 51chromium release assay. The levels of the cytotoxic activity were evaluated for potential prognostic significance.The mean cytotoxic activities of peripheral blood lymphocytes against K562 cells, T24 cells and autologous tumor cells were 37.2%, 19.8% and 9.7%, respectively, using an effector-to-target cell ratio of 40:1. Based on the analysis, patients with bladder tumors were divided into 2 groups of high (greater than the mean value) and low (less than the mean value) cytotoxic activity. The magnitude of the anti-K562 or anti-T24 cytotoxic activity did not correlate with the 5-year survival rate or the postoperative disease-free period. In contrast, bladder tumor patients with high anti-autologous cytotoxic activity had higher disease-specific survival rates and a longer postoperative tumor-free interval compared to those with low activity during the 5-year follow-up. In addition, similar analysis of the data at an effector-to-target cell ratio of 20:1 revealed that patients with high anti-autologous tumor cytotoxic activity also had a higher survival rate and a longer postoperative tumor-free period than those with low activity. No statistical differences were observed in patient age and sex, as well as the size, number, histological grade and stage of bladder tumors between patients with high and low anti-autologous tumor cytotoxic activity. The anti-autologous tumor cytotoxic activity was not paralleled with either anti-K562 or anti-T24 cytotoxic activity.These results suggest that anti-autologous tumor cytotoxic activity of peripheral blood lymphocytes might be a significant and independent prognostic indicator in patients with bladder tumors, and that the autologous tumor cell killing system might have an important role in the immune surveillance against bladder tumors.