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The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma.

By Ghada Kchour, SA Rezaee, Reza Farid, Akram Ghantous, Houshang Rafatpanah, Mahdi Tarhini, Mohamad-Mehdi Kooshyar, Hiba El Hajj, Fadwa Berry, Mohamad Mortada, Roudaina Nasser, Abbas Shirdel, Zeina Dassouki, Mohamad Ezzedine, Hossein Rahimi, Ardeshir Ghavamzadeh, Hugues De Thé, Olivier Hermine, Mahmoud Mahmoudi and Ali Bazarbachi

Abstract

International audienceBACKGROUND: HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN. RESULTS: Here we assessed Th1/Th2/Treg cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a Treg/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4+CD25+ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4+CD25+ cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30. CONCLUSIONS: The observed shift from a Treg/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections

Topics: Arsenic, Interferon, Zidovudine, HTLV-I, ATL, Cytokines, Immune deficiency, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Publisher: BioMed Central
Year: 2013
DOI identifier: 10.1186/1742-4690-10-91
OAI identifier: oai:HAL:inserm-00868737v1
Provided by: Hal-Diderot

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