Z. Reiter et Mw. Taylor, INTERLEUKIN-2 PROTECTS HAIRY LEUKEMIC-CELLS FROM LYMPHOKINE-ACTIVATEDKILLER CELL-MEDIATED CYTOTOXICITY, Cancer research, 53(15), 1993, pp. 3555-3560
Interleukin 2 (IL-2) activates natural killer cells and generates lymp
hokine-activated killer (LAK) cell-mediated cytotoxicity. In ''adoptiv
e immunotherapy,'' a combination of LAK administration and IL-2 infusi
on was found to be effective therapy for some tumors and ineffective f
or others. Here we report a novel function for IL-2, its ability to pr
otect tumor cells (cell lines obtained from hairy cell leukemia patien
ts) against LAK activity. The protective effect induced by IL-2 is sim
ilar to that induced by interferon (IFN). Protection by both cytokines
requires new mRNA/protein synthesis; both IL-2 and IFN reduce the abi
lity of tumor target cells to trigger LAK effector cells following bin
ding between these two types of cells. However, endogenous IFN is not
the mediator of the IL-2 protective effect against LAK activity since
monoclonal antibodies against IFN-alpha and IFN-gamma did not abolish
the protective effect of IL-2. In addition, IL-2 does not induce the e
xpression of class I major histocompatibility complex antigens on the
target cell surface, believed to be the signal for the IFN-induced pro
tection against natural killer and LAK activities. Finally, leukemic c
ells resistant to IFN-alpha did respond to IL-2 treatment and became l
ess sensitive to LAK cytotoxicity. Thus the ability of IL-2 to protect
tumor cells from LAK activity may explain the lack of response to ado
ptive immunotherapy in tumors that express the IL-2 receptor.