Fiche publication
Date publication
mai 2021
Journal
Haematologica
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MARCAIS Ambroise
Tous les auteurs :
El Hajj H, Hleihel R, El Sabban M, Bruneau J, Zaatari G, Cheminant M, Marçais A, Akkouche A, Hasegawa H, Hall W, De Thé H, Hermine O, Bazarbachi A
Lien Pubmed
Résumé
Adult T cell leukemia/lymphoma (ATL) is associated to chronic human T cell leukemia virus type 1 (HTLV-1) infection and carries a poor prognosis. Arsenic trioxide (AS) and interferon-alpha (IFNα) together selectively trigger Tax viral oncoprotein degradation and cure Tax-driven murine ATL. AS/IFNα/zidovudine treatment achieves a high response rate in patients with chronic ATL. Interleukin 10 (IL-10) is an immuno-suppressive cytokine whose expression is activated by Tax. Here we show that, in ATL, AS/IFNα-induced abrogation of leukemia initiating cell activity requires IL-10 expression shutoff. Loss of IL-10 secretion drives production of inflammatory cytokines by the microenvironment, followed by innate immunity-mediated clearance of Taxdriven leukemic cells. Accordingly, anti-IL-10 monoclonal antibodies significantly increased the efficiency of AS/IFNα therapy. These results emphasize the sequential targeting of malignant ATL cells and their immune microenvironment in leukemia initiating cell (LIC) eradication and provide a strong rational to test AS/IFNα/anti-IL10 combination in ATL.
Mots clés
Adult, Animals, Human T-lymphotropic virus 1, Humans, Immunity, Innate, Interferon-alpha, Interleukin-10, genetics, Leukemia-Lymphoma, Adult T-Cell, drug therapy, Mice, Tumor Microenvironment
Référence
Haematologica. 2021 05 1;106(5):1443-1456
