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 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.
Provinciali
M
M
Gerontological Research Department, Italian National Research Centers on Aging (INRCA), Ancona, Italy. m.provinciali@inrca.it
Di Stefano
G
G
Stronati
S
S
Fabris
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D002453:Cell Cycle; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000628:therapy
D015703:Antigens, CD; D007376:Interleukin-2