Interleukin 2 protects hairy leukemic cells from lymphokine-activated killer cell-mediated cytotoxicity

Interleukin 2 (IL-2) activates natural killer cells and generates lymphokine-activated killer (LAK) cell-mediated cytotoxicity. In "adoptive immunotherapy," a combination of LAK administration and IL-2 infusion was found to be effective therapy for some tumors and ineffective for others. Here we report a novel function for IL-2, its ability to protect tumor cells (cell lines obtained from hairy cell leukemia patients) against LAK activity. The protective effect induced by IL-2 is similar to that induced by interferon (IFN). Protection by both cytokines requires new mRNA/protein synthesis; both IL-2 and IFN reduce the ability of tumor target cells to trigger LAK effector cells following binding 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 expression of class I major histocompatibility complex antigens on the target cell surface, believed to be the signal for the IFN-induced protection against natural killer and LAK activities. Finally, leukemic cells resistant to IFN-alpha did respond to IL-2 treatment and became less sensitive to LAK cytotoxicity. Thus the ability of IL-2 to protect tumor cells from LAK activity may explain the lack of response to adoptive immunotherapy in tumors that express the IL-2 receptor.