Membrane-bound Fas (Apo-1/CD95) ligand on leukemic cells: A mechanism of tumor immune escape in leukemia patients

There is evidence from bone marrow transplantation that T cells may be invo lved in the immunologic control of leukemia. But many patients relapse desp ite a potent graft-versus-leukemia effect mediated by allogeneic T cells. T he expression of the Fast protein has been suggested as a mechanism of tumo r immune escape. We, therefore, evaluated the capacity of leukemic cells fr om patients with acute or chronic myelogenous leukemia to escape the alloge neic or autologous immune response by bearing the Fast molecule. Although a lmost all leukemic cells express the 37-kD form of Fast, only 54% of acute myeloblastic leukemia and 27% of chronic myeloid leukemia (CML) cells bore a Fast with killing properties, as assessed by the ability of leukemic cell s to cause the apoptosis of a Fas-sensitive target cell line or autologous activated T cells in 3 tested leukemic cases. Experiments with a recombinan t Fas-Fc molecule confirmed the role of Fas/FasL in leukemic-mediated cell death. Only CML leukemic cells from certain individuals contained the 26-kD truncated form of Fast. Thus, myeloid leukemic cells from some, but not al l patients can set up a mechanism of immune escape involving the Fas/FasL p athway. This leukemic escape may have implications for patients eligible fo r adoptive cellular immunotherapy, (C) 1999 by The American Society of Hema tology.