SIGNIFICANCE OF CYTOTOXIC ACTIVITY OF PERIPHERAL-BLOOD LYMPHOCYTES AGAINST AUTOLOGOUS TUMOR-CELLS IN PATIENTS WITH BLADDER-CANCER

Cell-mediated immunity is an important and central mechanism of host r esistance to cancer. Most reported studies have used cultured tumor ce ll lines as targets to assess antitumor cell-mediated cytotoxicity. Ho wever, it is difficult to translate the data generated from the cytoto xic activity against cultured tumor cell lines to cytotoxicity against autologous tumors. In a recent study, we have reported on the prognos tic significance of circulating cytotoxic lymphocytes against autologo us armor cells in patients with bladder cancer. In this study, we exam ined whether established bladder cancer cell line like T24 or NK-sensi tive K562 target cells can be substituted for autologous bladder cance r cells. The cytotoxic activity of peripheral blood lymphocytes (PBL) against freshly isolated autologous tumor cells, the T24 human bladder cancer cell line and the NK-sensitive K562 human myelogenous leukemia cell line was studied in 63 patients with primary initial bladder can cer by a 12-h Cr-51 release assay. The mean percent cytotoxic activity of PBL directed against autologous tumor cells, T24 cells and K562 ce lls were 11.3%, 18.2% and 29.4%, respectively, using an E:T of 40:1. T he cytotoxic activity against T24 cells in patients with bladder cance l was higher than that in normal individuals. The anti-K562 and the an ti-T24 cytotoxic activities in patients with low-stage or low-grade bl adder cancer were relatively higher than those in patients with high-s tage or high-grade cancer, but not statistically significant. There wa s no correlation between the anti-autologous tumor cytotoxic activity and either the histologic grade or stage in patients with bladder canc er. The extent of the anti-autologous tumor cytotoxic activity was not paralleled with that of either the anti-K562 or the anti-T24 cytotoxi c activity. In contrast the anti-K562 cytotoxic activity correlated po sitively with the anti-T24 cytotoxic activity. Separation of PBL revea led that the anti-K562 and the anti-T24 cytotoxic activities were medi ated mainly by the NK cells, whereas the anti-autologous tumor cytotox ic activity was mediated by both the NK cells and the T lymphocytes. T hese findings demonstrate that cytotoxicity against T24 or K562 cells is not of prognostic value. The magnitude of the anti-autologous tumor cytotoxic activity of PBL derived from bladder cancer patients. might represent an independent and important immunological parameter to mon itor disease progression.