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Lysis of neuroblastoma cell lines by human natural killer cells activated
by interleukin-2 and interleukin-12
AR Rossi, F Pericle, S Rashleigh, J Janiec and JY Djeu
Department of Pediatrics, University of Florida, Gainsville.
Neuroblastoma is the most common extracranial, solid tumor in children.
Despite intensive chemotherapy and bone marrow transplantation, the 5- year
projected survival rate is 20% to 25%. In vitro studies have shown enhanced
natural killer cell (NK) lysis of tumor cells after exposure of NK cells to
interleukin-2 (IL-2). In vivo studies have demonstrated similar immunologic
effects but have also revealed severe toxicities associated with the use of
IL-2. IL-12 is a newly described cytokine that has several properties,
including the ability to act synergistically with IL-2 in generating
lymphokine-activated killer cells (LAK) against known tumor targets. We
investigated the role of IL- 12 in the generation of peripheral blood
mononuclear cell (PBMC) lysis of neuroblastoma cell lines. PBMC were
activated with IL-12 alone and in combination with IL-2. Whereas IL-12
alone produced only modest enhancement of NK cell cytotoxicity, the
combination of IL-2 and IL-12 was most effective in activating NK cell
lysis of neuroblastoma cell lines. Further, we showed that large granular
lymphocytes were the effector cells involved in target cell lysis. Finally,
the CD18 molecule was shown to be critical in the lysis of neuroblastoma
cells by activated PBMC.
Volume 83,
Issue 5,
pp. 1323-1328,
03/01/1994
Copyright © 1994 by The American Society of Hematology
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