{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:29:35Z","timestamp":1794047375278,"version":"4.8.0"},"reference-count":36,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"5","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>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 (IFN\u03b1) together selectively trigger Tax viral oncoprotein degradation and cure Tax-driven murine ATL. AS\/IFN\u03b1\/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\/IFN\u03b1-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\/IFN\u03b1 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\/IFN\u03b1\/anti-IL10 combination in ATL.<\/jats:p>","DOI":"10.3324\/haematol.2020.264523","type":"journal-article","created":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T13:47:43Z","timestamp":1613051263000},"page":"1443-1456","source":"Crossref","is-referenced-by-count":15,"title":["Loss of interleukin-10 activates innate immunity to eradicate adult T-cell leukemia-initiating cells"],"prefix":"10.3324","volume":"106","author":[{"given":"Hiba","family":"El Hajj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Hleihel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"El Sabban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bruneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazi","family":"Zaatari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Cheminant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambroise","family":"Mar\u00e7ais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdou","family":"Akkouche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugues","family":"De Th\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Hermine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Bazarbachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2021,2,11]]},"reference":[{"key":"21396","unstructured":"Takatsuki K. [Adult T-cell leukemia]. Nihon Rinsho. 1978;Suppl:1646-1647."},{"key":"21397","doi-asserted-by":"publisher","DOI":"10.1038\/294268a0"},{"key":"21398","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.69.5.2863-2868.1995"},{"key":"21399","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401624"},{"key":"21400","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.537"},{"key":"21401","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.11.8852-8860.1998"},{"key":"21402","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.475"},{"key":"21403","doi-asserted-by":"publisher","DOI":"10.1038\/nm1389"},{"key":"21404","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.12469.2"},{"key":"21405","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-04-572750"},{"key":"21406","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1715724115"},{"key":"21407","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13302"},{"key":"21408","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.0669"},{"key":"21409","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-345702"},{"key":"21410","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506293322603"},{"key":"21411","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506293322604"},{"key":"21412","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017011106"},{"key":"21413","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.1.278"},{"key":"21414","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.13.3762"},{"key":"21415","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-211821"},{"key":"21416","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101095"},{"key":"21417","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-020-0513-y"},{"key":"21418","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006861"},{"key":"21419","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-10-91"},{"key":"21420","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006597"},{"key":"21421","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2001-12-0207"},{"key":"21422","doi-asserted-by":"publisher","DOI":"10.3791\/4105"},{"key":"21423","unstructured":"El-Sabban ME, Nasr R, Dbaibo G, et al. Arsenic-interferon-alpha-triggered apoptosis in HTLV-I transformed cells is associated with tax down-regulation and reversal of NF-kappa B activation. 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