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H. El Hajj et al.
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Figure 6. Combination of an anti-interleukin-10 monoclonal antibody, arsenic and interferon abrogates adult T-cell leukemic-initiating cell activity. (A) Kaplan-Meier analysis of overall survival of primary SCID mice injected with 106 unsorted spleen cells and treated with an anti-interleukin (IL)-10 antibody (blue line; n=5), arsenic trioxide (AS)/ interferon alpha (IFNα) (red line; n=7) or the triple combination AS/IFNα/anti-IL-10 antibody (green line; n=5) or left untreated (control; black line; n=5). (B) Survival of secondary recipient SCID mice injected with 106 unsorted spleen cells derived from primary SCID mice with adult T-cell leukemia/lymphoma (ATL) treated with an anti-IL-10 antibody (blue line; n=5), AS/IFNα (red line; n=6) or AS/IFNα/anti-IL-10 antibody (green line; n=10) or untreated controls (black line; n=10). Secondary SCID mice injected with 106 spleen cells derived from primary ATL SCID treated with AS/IFNα/anti-IL-10 were treated with clodronate (light blue line; n=5) or anti-NK1.1 (purple line; n=5) starting on day 3 after injection of leukemic cells. (C) Proposed model for therapy-induced ATL cure: ATL cells depend on IL-10 sig- naling to escape from the innate immune system. Treatment with AS/IFNα induces Tax degradation, resulting in decreased IL-10 production, activation of NK cells and macrophages and innate immunity-mediated abrogation of ATL LIC activity.
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haematologica | 2021; 106(5)