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

Ghada Kchour (1) , Sa Rahim Rezaee (2) , Reza Farid (3) , Akram Ghantous (4) , Houshang Rafatpanah (3) , Mahdi Tarhini (5) , Mohamad-Mehdi Kooshyar (6) , Hiba El Hajj (7) , Fadwa Berry (1) , Mohamad Mortada (1) , Roudaina Nasser (3) , Abbas Shirdel (3) , Zeina Dassouki (3) , Mohamad Ezzedine (1) , Hossein Rahimi (3) , Ardeshir Ghavamzadeh (8) , Hugues de Thé (9) , Olivier Hermine (10) , Mahmoud Mahmoudi (3) , Ali Bazarbachi (3)

1 LU / ULB - الجامعة اللبنانية [بيروت] = Lebanese University [Beirut] = Université libanaise [Beyrouth]
2 Microbiology and Virology Research Center
3 Immunology Research Centre Bu-Ali Research Institute
4 LAU - Lebanese American University
5 Faculty of Nursing Sciences
6 Department of Internal Medicine [Mashhad]
7 Department of Internal Medicine
8 Hematology-Oncology and Stem Cell Research Center
9 PVM (UMR_7151) - Pathologie et virologie moléculaire
10 CHRI - Cytokines, hématopoïèse et réponse immune

BACKGROUND: 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.

Mots clés: Arsenic; Interferon; Zidovudine; HTLV-I; ATL; Cytokines; Immune deficiency

Domaines: Maladies infectieuses

Ghada Kchour, Sa Rahim Rezaee, Reza Farid, Akram Ghantous, Houshang Rafatpanah, et al.. The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma.. Retrovirology, 2013, 10 (1), pp.91. ⟨10.1186/1742-4690-10-91⟩. ⟨inserm-00868737⟩