Loss of interleukin-10 activates innate immunity to eradicate adult T-cell leukemia-initiating cells - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Haematologica Année : 2021

Loss of interleukin-10 activates innate immunity to eradicate adult T-cell leukemia-initiating cells

Ambroise Marçais
  • Fonction : Auteur

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.

Dates et versions

hal-04055411 , version 1 (02-04-2023)

Identifiants

Citer

Hiba El Hajj, Rita Hleihel, Marwan El Sabban, Julie Bruneau, Ghazi Zaatari, et al.. Loss of interleukin-10 activates innate immunity to eradicate adult T-cell leukemia-initiating cells. Haematologica, 2021, 106 (5), pp.1443-1456. ⟨10.3324/haematol.2020.264523⟩. ⟨hal-04055411⟩
13 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More