@article {475,
	title = {Enhanced human lymphokine-activated killer cell function after brief exposure to granulocyte-macrophage-colony stimulating factor},
	journal = {Cancer},
	volume = {76},
	number = {7},
	year = {1995},
	pages = {1253-60},
	type = {Journal Article},
	abstract = {Lymphokine-activated killer (LAK) cell function can be generated in peripheral blood mononuclear cells (PBMC) after brief exposure of high dose interleukin-2 (IL-2) over the course of 1 or 2 days{\textquoteright} culture in plain culture medium (IL-2-pulsed PBMC). The aim of the present study was to investigate the ability of granulocyte-macrophage-colony stimulating factor (GM-CSF) to augment LAK induction in low dose IL-2-pulsed PBMC derived from patients with cancer undergoing immunotherapy with IL-2.|Peripheral blood mononuclear cells were collected from patients with cancer receiving a 5-day cycle of local (intraperitoneal or intrapleural) infusions with IL-2. The cells were incubated with IL-2 in the presence or absence of GM-CSF for 1 hour and then tested as effectors against allogeneic tumor cells and LAK-sensitive cell lines.|Granulocyte-macrophage-colony stimulating factor at doses between 10 and 100 ng/ml was synergized with low dose IL-2 (100 IU/ml) in the generation of LAK activity in PBMC. Lymphokine-activated killer cell-mediated cytotoxicity derived from PBMC cultures incubated with IL-2 and GM-CSF was significantly higher (up to three-fold) compared with that generated with IL-2 alone. The GM-CSF-induced enhanced LAK activity was maintained when tested at day 5. GM-CSF increased the percentages of IL-2 receptor (R) positive (+) and CD8+ cells in the IL-2-pulsed PBMC. In contrast to CD56+ cells, highly purified CD8+ cells isolated from PBMC pulsed with IL-2 and GM-CSF responded with increased LAK activity, thus representing the cell-type that mediates the augmenting effect of GM-CSF. Major histocompatibility complex (MHC) molecules or the CD3 surface antigens were not involved in the GM-CSF-mediated enhancement of LAK induction because anti-MHC class I and class II monoclonal antibodies (MoAb) or MoAb against the CD3 molecules remained without any effect in this system. The GM-CSF-mediated LAK-enhancement was IL-2-dependent because MoAb against IL-2 receptor completely inhibited the generation of LAK activity.|The use of GM-CSF for the enhancement of IL-2-induced LAK activity in 1 hour cultures may improve clinical results in cancer immunotherapy. In addition, implementation of this procedure could eliminate the high cost of cell culture which usually accompanies IL-2/LAK cell therapy as well as eliminate the known toxic side effects associated with this kind of therapy.},
	keywords = {Adolescent Adult Aged Antigens, Adoptive Interleukin-2 Killer Cells, CD56 CD8-Positive T-Lymphocytes Cells, Cultured Child Child, Immunologic Female Granulocyte-Macrophage Colony-Stimulating Factor Humans Immunotherapy, Interleukin-2, Lymphokine-Activated Male Receptors, Preschool Cytotoxicity},
	issn = {0008-543X},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/8630906},
	author = {Baxevanis, C. N. and Dedoussis, G. V. and Papadopoulos, N. G. and Missitzis, I. and Beroukas, C. and Stathopoulos, G. P. and Papamichail, M.}
}
