GM-CSF ENHANCES IL-2-ACTIVATED NATURAL-KILLER-CELL LYSIS OF CLONOGENIC AML CELLS BY UP-REGULATING TARGET-CELL EXPRESSION OF ICAM-1

Acute myeloid leukemia (AML) cells express the surface adhesion protei ns intercellular adhesion molecule-1 (ICAM-1, CD54) and lymphocyte fun ction associated molecule-3 (LFA-3, CD58). Exposure to the myeloid gro wth-promoting cytokine granulocyte-macrophage colony-stimulating facto r (GM-CSF) upregulates expression of ICAM-1 and LFA-3 on AML cells but does not increase their sensitivity to lysis by interleukin-2-activat ed natural killer cells (LAK) in Cr-51 assays. However when AML cells are exposed to GM-CSF prior to incubation with LAK, their subsequent c lonogenic activity is significantly reduced. If a blocking antibody to ICAM-1 is added during the incubation period of AML with LAK, the inh ibitory effect is completely ablated. A less pronounced effect is obse rved with an antibody to LFA-3. ICAM-1 is expressed on a greater propo rtion of CD34+ than CD34- AML cells and exposure to GM-CSF induces a s ignificantly greater upregulation of ICAM-1 on leukemic CD34+ cells th an their CD34- counterparts. These data suggest that the inhibitory ef fect of IL-2-activated natural killer cells on clonogenic AML cells is mediated principally via the lymphocyte function associated molecule- 1 interaction. Interleukin-2 upregulates LFA-1 natural killer cells. S imultaneous administration of effector cell activators such as IL-2 an d target cell modulators such as GMCSF may have a therapeutic benefit in patients with minimal residual myeloid leukemia.