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 involved in the immunologic control of leukemia. But many patients relapse despite a potent graft-versus-leukemia effect mediated by allogeneic T cells. The expression of the FasL protein has been suggested as a mechanism of tumor immune escape. We, therefore, evaluated the capacity of leukemic cells from patients with acute or chronic myelogenous leukemia to escape the allogeneic or autologous immune response by bearing the FasL molecule. Although almost all leukemic cells express the 37-kD form of FasL, only 54% of acute myeloblastic leukemia and 27% of chronic myeloid leukemia (CML) cells bore a FasL with killing properties, as assessed by the ability of leukemic cells to cause the apoptosis of a Fas-sensitive target cell line or autologous activated T cells in 3 tested leukemic cases. Experiments with a recombinant 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 FasL. Thus, myeloid leukemic cells from some, but not all patients can set up a mechanism of immune escape involving the Fas/FasL pathway. This leukemic escape may have implications for patients eligible for adoptive cellular immunotherapy.
Buzyn
A
A
INSERM Unité 445, ICGM, Hôpital Cochin; INSERM E 99-22, Faculté de Médecine Bichat, Paris, France. buzyn@icgm.cochin.inserm.fr
Petit
F
F
Ostankovitch
M
M
Figueiredo
S
S
Varet
B
B
Guillet
J G
JG
Ameisen
J C
JC
Estaquier
J
J
D016923:Cell Death / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D007938:Leukemia / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D019014:fas Receptor