GENERATION OF HUMAN LYMPHOKINE-ACTIVATED KILLER-CELLS FOLLOWING AN IL-2 PULSE IN ELDERLY CANCER-PATIENTS

The toxicity of high-dose interleukin 2 (IL-2) treatments limits its u se in tumour therapies, particularly in older age groups, characterize d by a reduced tolerance to antineoplastic therapies, Here, we evaluat ed the possibility to induce cytotoxic lymphokine-activated killer (LA K) cells through a brief exposure (1-h pulse) of peripheral blood mono nuclear cells (PBMC) from elderly cancer patients to high concentratio ns of IL-2, The cytotoxic activity, phenotype, apoptosis, and cell cyc le phase of IL-2 pulsed PBMC were determined and compared with those o f non-pulsed PBMC cultured continuously in IL-2, Significant levels of LAK cytotoxicity were obtained in pulsed PBMC from all patients exami ned. The mean values of lytic activity on day 6 of culture were lower, even if not significantly, in pulsed than non-pulsed cultures, The pu lsed cells were phenotypically similar to non-pulsed lymphocytes with regards to the expression of CD3, CD4, CD8, CD16, and CD56 antigens, T he induction of activation markers, like CD25 and CD122 IL-2 receptors and CD71 transferrin receptor, was also comparable in pulsed and non- pulsed cultures, When a lower cytotoxicity was found in pulsed culture s, a lower number of CD54(+) (ICAM-1) cells was also found, LAK cell c ytotoxicity and number of CD54 cells were significantly correlated, No difference was found between pulsed and non-pulsed cultures in their cell cycle phase or in the percentage of apoptotic cells, Autologous p lasma did not inhibit the differentiation of pulsed PBMC into LAK cell s, The IL-2 pulse of PBMC from healthy young donors resulted in the in duction of LAK cytotoxicity as observed in elderly cancer patients, Th e results demonstrate the effectiveness of IL-2 pulse to generate cyto toxic LAK cells in elderly cancer patients suggesting the potential ap plication of pulsing procedures to treatment of older age groups. (C) 1998 Academic Press Limited.