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Lymphoma

Stimulation of non-Hodgkin's lymphoma via HVEM: an alternate and safe way to increase Fas-induced apoptosis and improve tumor immunogenicity

Abstract

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.

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Acknowledgements

This work was funded in part by the ‘Groupement Entreprise Français Lutte Cancer’, the ‘Association pour la Recherche contre le Cancer’, the ‘Ligues contre le Cancer des Bouches-du-Rhône et du Var’, the ‘Ligue contre le Cancer de Bastia’, the ‘Fédération Nationale des Centres de Lutte Contre le Cancer’, the ‘Etablissement Français des Greffes’ and the ‘Fondation Contre la Leucémie’, the ‘Fondation pour la Recherche Médicale’ and the ‘Institut SmithKline Beecham, Paris’.

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Costello, R., Mallet, F., Barbarat, B. et al. Stimulation of non-Hodgkin's lymphoma via HVEM: an alternate and safe way to increase Fas-induced apoptosis and improve tumor immunogenicity. Leukemia 17, 2500–2507 (2003). https://doi.org/10.1038/sj.leu.2403175

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