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  • Oral presentation
  • Open Access

The combination of arsenic, interferon-alpha, and zidovudine restores an “immunocompetent-like” micro-environment in patients with adult T-cell leukemia lymphoma

  • 1,
  • 2,
  • 3,
  • 4,
  • 3,
  • 5,
  • 6,
  • 7,
  • 1,
  • 7,
  • 6,
  • 7,
  • 1,
  • 6,
  • 8,
  • 9,
  • 10,
  • 3 and
  • 7
Retrovirology201411 (Suppl 1) :O4

https://doi.org/10.1186/1742-4690-11-S1-O4

  • Published:

Keywords

  • Arsenic
  • Zidovudine
  • Arsenic Trioxide
  • Dismal Prognosis
  • Cytokine Gene Expression

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. 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. 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.

Authors’ Affiliations

(1)
Department of Biology , Faculty of Sciences, Lebanese University, Hadath, Lebanon
(2)
Microbiology and Virology Research Center, Bu-Ali Research institute, Mashhad University of Medical Sciences, Mashhad, Iran
(3)
Immunology Research Centre Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
(4)
School of Arts and Sciences, Lebanese American University, Lebanon
(5)
Faculty of Nursing Sciences, Islamic University, Lebanon
(6)
Department of Internal Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
(7)
Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
(8)
Tehran University of Medical Sciences, Tehran, Iran
(9)
INSERM UMR 944 and CNRS UMR 7212, Hôpital Saint Louis, Paris, France
(10)
CNRS UMR 8147, Hôpital Necker, Paris, France

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