TY - JOUR
T1 - Generation of human lymphokine-activated killer cells following an IL-2 pulse in elderly cancer patients
AU - Provinciali, Mauro
AU - Di Stefano, Giuseppina
AU - Stronati, Stefania
AU - Fabris, Nicola
PY - 1998/2
Y1 - 1998/2
N2 - The toxicity of high-dose interleukin 2 (IL-2) treatments limits its use in tumour therapies, particularly in older age groups, characterized by a reduced tolerance to antineoplastic therapies. Here, we evaluated the possibility to induce cytotoxic lymphokine-activated killer (LAK) cells through a brief exposure (1-h pulse) of peripheral blood mononuclear cells (PBMC) from elderly cancer patients to high concentrations of IL-2. The cytotoxic activity, phenotype, apoptosis, and cell cycle phase of IL-2 pulsed PBMC were determined and compared with those of non-pulsed PBMC cultured continuously in IL-2. Significant levels of LAK cytotoxicity were obtained in pulsed PBMC from all patients examined. The mean values of lytic activity on day 6 of culture were lower, even if not significantly, in pulsed than non-pulsed cultures. The pulsed cells were phenotypically similar to non-pulsed lymphocytes with regards to the expression of CD3, CD4, CD8, CD16, and CD56 antigens. The 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 cultures, a lower number of CD54+ (ICAM-1) cells was also found, LAK cell cytotoxicity 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 plasma did not inhibit the differentiation of pulsed PBMC into LAK cells. The IL-2 pulse of PBMC from healthy young donors resulted in the induction of LAK cytotoxicity as observed in elderly cancer patients. The results demonstrate the effectiveness of IL-2 pulse to generate cytotoxic LAK cells in elderly cancer patients suggesting the potential application of pulsing procedures to treatment of older age groups.
AB - The toxicity of high-dose interleukin 2 (IL-2) treatments limits its use in tumour therapies, particularly in older age groups, characterized by a reduced tolerance to antineoplastic therapies. Here, we evaluated the possibility to induce cytotoxic lymphokine-activated killer (LAK) cells through a brief exposure (1-h pulse) of peripheral blood mononuclear cells (PBMC) from elderly cancer patients to high concentrations of IL-2. The cytotoxic activity, phenotype, apoptosis, and cell cycle phase of IL-2 pulsed PBMC were determined and compared with those of non-pulsed PBMC cultured continuously in IL-2. Significant levels of LAK cytotoxicity were obtained in pulsed PBMC from all patients examined. The mean values of lytic activity on day 6 of culture were lower, even if not significantly, in pulsed than non-pulsed cultures. The pulsed cells were phenotypically similar to non-pulsed lymphocytes with regards to the expression of CD3, CD4, CD8, CD16, and CD56 antigens. The 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 cultures, a lower number of CD54+ (ICAM-1) cells was also found, LAK cell cytotoxicity 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 plasma did not inhibit the differentiation of pulsed PBMC into LAK cells. The IL-2 pulse of PBMC from healthy young donors resulted in the induction of LAK cytotoxicity as observed in elderly cancer patients. The results demonstrate the effectiveness of IL-2 pulse to generate cytotoxic LAK cells in elderly cancer patients suggesting the potential application of pulsing procedures to treatment of older age groups.
KW - Aging
KW - Cancer
KW - IL-2 pulse
KW - LAK cells
UR - http://www.scopus.com/inward/record.url?scp=0032007311&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032007311&partnerID=8YFLogxK
U2 - 10.1006/cyto.1997.0265
DO - 10.1006/cyto.1997.0265
M3 - Article
C2 - 9512903
AN - SCOPUS:0032007311
VL - 10
SP - 132
EP - 139
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 2
ER -