Stimulation of non-Hodgkin's lymphoma via HVEM: an alternate and safe way to increase Fas-induced apoptosis and improve tumor immunogenicity
| Autor: | R W Sweet, Danielle Sainty, Françoise Mallet, J-M Schiano de Colella, Régis Costello, Alemseged Truneh, Daniel Olive, B Barbarat |
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| Rok vydání: | 2003 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research Herpesvirus entry mediator Gene Expression Apoptosis Lymphoma Mantle-Cell Ligands Transfection Receptors Tumor Necrosis Factor medicine Cell Adhesion Humans fas Receptor CD40 Antigens B-Lymphocytes CD40 biology Cell Death business.industry Lymphoma Non-Hodgkin Hematology Dendritic Cells medicine.disease Non-Hodgkin's lymphoma Lymphoma Lymphotoxin Oncology Immunology Cancer research biology.protein Interleukin-2 Receptors Virus Tumor necrosis factor alpha Mantle cell lymphoma Immunotherapy Lymphocyte Culture Test Mixed business Receptors Tumor Necrosis Factor Member 14 Cell Division |
| Zdroj: | Leukemia. 17(12) |
| ISSN: | 0887-6924 |
| Popis: | Stimulation by CD40 ligand (L) improves B-cell malignancy immunogenicity, and also induces proliferative signals. To avoid these tumorigenic effects, we studied an alternate way of tumor-cell stimulation by homologous to lymphotoxin, inducible expression, competing for GpD of herpesvirus, which binds to the herpesvirus entry mediator (HVEM), and is expressed on T-lymphocytes (LIGHT), the ligand for HVEM, a new member of the tumor necrosis factor (TNF)/TNF-receptor (-R) family. HVEM is constitutively expressed on the surface of tumor B cells. We focused our attention on mantle cell lymphoma, a subtype of B-cell malignancy of poor prognosis. Triggering by LIGHT, in contrast to CD40L stimulation, did not increase lymphoma proliferation nor decrease chemotherapy entrance. We observed an upregulation of the TNFR apoptosis-inducing ligand Fas, and in contrast to CD40L-induced protection, an enhancement of lymphoma sensitivity to Fas-induced apoptosis. LIGHT triggering increased lymphoma cell recognition in a mixed lymphocyte response. In conclusion, LIGHT-mediated triggering renders B-cell lymphomas more immunogeneic and sensitive to apoptosis, without inducing proliferation. Since LIGHT triggering also enhances the functions of T-lymphocytes and dendritic cells, it could be a unique way to restore an efficient cancer control by its pleiotropic effects on immune effectors and tumor cells. |
| Databáze: | OpenAIRE |
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