Membrane-Bound Fas (Apo-1/CD95) Ligand on Leukemic Cells: A Mechanism of Tumor Immune Escape in Leukemia Patients

Abstract

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.

Serum levels of sCD137 (4‐1BB) ligand are prognostic factors for progression in acute myeloid leukemia but not in non‐Hodgkin's lymphoma

“…Moreover, it could be shown by others and us, that CD178 is expressed on acute leukemia cell lines and primary AML cells and influences the interaction between leukemia cells with cocultured T‐cells . This could play a role in the mediation of the immune escape of leukemic cells (27, 28). It has also been shown that release of CD178 as a soluble form from the cell surface reduces its ability to induce apoptosis in CD95‐sensitive target cell (33).…”

“…In MDS, expression of CD178 has been shown to inhibit the growth of hematopoietic progenitor cells, to influence anemia, transfusion requirements and survival of patients, and CD178 expression is involved in apoptosis‐induction in MDS cells (23–26). It was recently demonstrated that CD178 is expressed on acute leukemia cell lines and primary cells of patients, and expression of CD178 significantly alters the interaction of the leukemia cells with cocultured T cells suggesting that CD178 expression enables the immune escape of leukemia cells (27, 28). It has also been demonstrated that serum levels of soluble TNF family members like, e.g.…”

Role of CD95-activated caspase-1 processing of IL-1β in TCR-mediated proliferation of HIV-infected CD4+ T cells

“…Western blot analysis was done as previously described 39. Immunoblots were assessed for caspases using anti‐caspase‐3 (Pharmingen), anti‐caspase‐8 (5F7, Upstate Biotechnology, Lake Placid, NY), anti‐caspase‐1 p20 (CAL) anti‐caspase‐1 p10 (ALP) were kindly provided by C. Miossec (Aventis, Romainville, France), anti‐tubulin (KMX‐1, Boehringer Mannheim) was used as a control of loading.…”

Expressão de genes e proteínas anti-e-pró-apoptóticas em células precursoras da medula óssea e leucócitos do sangue periférico de pacientes portadores de policitemia vera

“…A elucidação dessas alterações pode colaborar com a escolha e/ou modulação do tratamento das doenças. Na PV, um defeito no controle de morte celular por apoptose pode causar o acúmulo de células eritróides sem a necessidade de EPO (FERNANDEZ-LUNA, 1999 (BUZYN et al, 1999).…”

“…As expressões aumentadas do FASL em células tumorais e leucêmicas constituem um dos mecanismos de escape dos clones leucêmicos à resposta imune anti-tumoral. Estes antígenos estão presentes na superfície de diferentes tipos de células neoplásicas, como por exemplo, células de melanoma, câncer de cólon, hepatocarcinoma, mieloma múltiplo e leucemias (BUZYN et al, 1999;ZEYTUN et al, 1997). Estas células tumorais e leucêmicas podem se ligar a linfócitos T ou células NK ativadas que expressam o antígeno Fas e conduzilas a apoptose, promovendo, desta forma, a inativação da resposta imune anti-tumoral.…”