The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma
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 triox...
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| Veröffentlicht in: | Retrovirology 2013-08, Vol.10 (1), p.91-91, Article 91 |
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| creator | Kchour, Ghada Rezaee, Rahim Farid, Reza Ghantous, Akram Rafatpanah, Houshang Tarhini, Mahdi Kooshyar, Mohamad-Mehdi El Hajj, Hiba Berry, Fadwa Mortada, Mohamad Nasser, Roudaina Shirdel, Abbas Dassouki, Zeina Ezzedine, Mohamad Rahimi, Hossein Ghavamzadeh, Ardeshir de Thé, Hugues Hermine, Olivier Mahmoudi, Mahmoud Bazarbachi, Ali |
| description | 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/T(reg) 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 T(reg)/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.
The observed shift from a T(reg)/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. |
| doi_str_mv | 10.1186/1742-4690-10-91 |
| format | Article |
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Here we assessed Th1/Th2/T(reg) 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 T(reg)/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.
The observed shift from a T(reg)/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.</description><identifier>ISSN: 1742-4690</identifier><identifier>EISSN: 1742-4690</identifier><identifier>DOI: 10.1186/1742-4690-10-91</identifier><identifier>PMID: 23962110</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adult ; Aged ; Analysis ; Arsenic ; Arsenic Trioxide ; Arsenicals - administration & dosage ; Bacterial infections ; Blood donors ; Cytokines ; Cytokines - genetics ; Disease ; Dosage and administration ; Drug therapy ; Drug therapy, Combination ; Female ; Gene expression ; Gene Expression Profiling ; Health aspects ; HTLV-I Infections - drug therapy ; HTLV-I Infections - immunology ; Human health and pathology ; Human T-lymphotropic virus 1 ; Humans ; Immunologic Factors - administration & dosage ; Immunology ; Infections ; Infectious diseases ; Interferon ; Interferon-alpha - administration & dosage ; Interleukins ; Internal medicine ; Leukemia ; Leukemia-Lymphoma, Adult T-Cell - drug therapy ; Leukemia-Lymphoma, Adult T-Cell - immunology ; Life Sciences ; Lymphoma ; Lymphomas ; Male ; Middle Aged ; Oxides - administration & dosage ; Physiological aspects ; Prognosis ; Prospective Studies ; RNA ; Statistical analysis ; T cells ; Thermal cycling ; Treatment Outcome ; Viral infections ; Zidovudine ; Zidovudine - administration & dosage</subject><ispartof>Retrovirology, 2013-08, Vol.10 (1), p.91-91, Article 91</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Kchour et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2013 Kchour et al.; licensee BioMed Central Ltd. 2013 Kchour et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b617t-a8a675aee365e21841a8a195256dde206725c29f2cc296540e9725175a82e09b3</citedby><cites>FETCH-LOGICAL-b617t-a8a675aee365e21841a8a195256dde206725c29f2cc296540e9725175a82e09b3</cites><orcidid>0000-0002-1113-4472 ; 0000-0002-7171-4997 ; 0000-0002-1069-0477 ; 0000-0003-2574-3874</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751834/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751834/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23962110$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-00868737$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Kchour, Ghada</creatorcontrib><creatorcontrib>Rezaee, Rahim</creatorcontrib><creatorcontrib>Farid, Reza</creatorcontrib><creatorcontrib>Ghantous, Akram</creatorcontrib><creatorcontrib>Rafatpanah, Houshang</creatorcontrib><creatorcontrib>Tarhini, Mahdi</creatorcontrib><creatorcontrib>Kooshyar, Mohamad-Mehdi</creatorcontrib><creatorcontrib>El Hajj, Hiba</creatorcontrib><creatorcontrib>Berry, Fadwa</creatorcontrib><creatorcontrib>Mortada, Mohamad</creatorcontrib><creatorcontrib>Nasser, Roudaina</creatorcontrib><creatorcontrib>Shirdel, Abbas</creatorcontrib><creatorcontrib>Dassouki, Zeina</creatorcontrib><creatorcontrib>Ezzedine, Mohamad</creatorcontrib><creatorcontrib>Rahimi, Hossein</creatorcontrib><creatorcontrib>Ghavamzadeh, Ardeshir</creatorcontrib><creatorcontrib>de Thé, Hugues</creatorcontrib><creatorcontrib>Hermine, Olivier</creatorcontrib><creatorcontrib>Mahmoudi, Mahmoud</creatorcontrib><creatorcontrib>Bazarbachi, Ali</creatorcontrib><title>The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma</title><title>Retrovirology</title><addtitle>Retrovirology</addtitle><description>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/T(reg) 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 T(reg)/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.
The observed shift from a T(reg)/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.</description><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Arsenic</subject><subject>Arsenic Trioxide</subject><subject>Arsenicals - administration & dosage</subject><subject>Bacterial infections</subject><subject>Blood donors</subject><subject>Cytokines</subject><subject>Cytokines - genetics</subject><subject>Disease</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Drug therapy, Combination</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Health aspects</subject><subject>HTLV-I Infections - drug therapy</subject><subject>HTLV-I Infections - immunology</subject><subject>Human health and pathology</subject><subject>Human T-lymphotropic virus 1</subject><subject>Humans</subject><subject>Immunologic Factors - administration & dosage</subject><subject>Immunology</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Interferon</subject><subject>Interferon-alpha - administration & dosage</subject><subject>Interleukins</subject><subject>Internal medicine</subject><subject>Leukemia</subject><subject>Leukemia-Lymphoma, Adult T-Cell - drug therapy</subject><subject>Leukemia-Lymphoma, Adult T-Cell - immunology</subject><subject>Life Sciences</subject><subject>Lymphoma</subject><subject>Lymphomas</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Oxides - administration & dosage</subject><subject>Physiological aspects</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>RNA</subject><subject>Statistical analysis</subject><subject>T cells</subject><subject>Thermal cycling</subject><subject>Treatment Outcome</subject><subject>Viral infections</subject><subject>Zidovudine</subject><subject>Zidovudine - 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immunology</topic><topic>Life Sciences</topic><topic>Lymphoma</topic><topic>Lymphomas</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Oxides - administration & dosage</topic><topic>Physiological aspects</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>RNA</topic><topic>Statistical analysis</topic><topic>T cells</topic><topic>Thermal cycling</topic><topic>Treatment Outcome</topic><topic>Viral infections</topic><topic>Zidovudine</topic><topic>Zidovudine - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kchour, Ghada</creatorcontrib><creatorcontrib>Rezaee, Rahim</creatorcontrib><creatorcontrib>Farid, Reza</creatorcontrib><creatorcontrib>Ghantous, Akram</creatorcontrib><creatorcontrib>Rafatpanah, Houshang</creatorcontrib><creatorcontrib>Tarhini, Mahdi</creatorcontrib><creatorcontrib>Kooshyar, Mohamad-Mehdi</creatorcontrib><creatorcontrib>El Hajj, Hiba</creatorcontrib><creatorcontrib>Berry, Fadwa</creatorcontrib><creatorcontrib>Mortada, Mohamad</creatorcontrib><creatorcontrib>Nasser, Roudaina</creatorcontrib><creatorcontrib>Shirdel, Abbas</creatorcontrib><creatorcontrib>Dassouki, Zeina</creatorcontrib><creatorcontrib>Ezzedine, Mohamad</creatorcontrib><creatorcontrib>Rahimi, Hossein</creatorcontrib><creatorcontrib>Ghavamzadeh, Ardeshir</creatorcontrib><creatorcontrib>de Thé, Hugues</creatorcontrib><creatorcontrib>Hermine, Olivier</creatorcontrib><creatorcontrib>Mahmoudi, Mahmoud</creatorcontrib><creatorcontrib>Bazarbachi, Ali</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Retrovirology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kchour, Ghada</au><au>Rezaee, Rahim</au><au>Farid, Reza</au><au>Ghantous, Akram</au><au>Rafatpanah, Houshang</au><au>Tarhini, Mahdi</au><au>Kooshyar, Mohamad-Mehdi</au><au>El Hajj, Hiba</au><au>Berry, Fadwa</au><au>Mortada, Mohamad</au><au>Nasser, Roudaina</au><au>Shirdel, Abbas</au><au>Dassouki, Zeina</au><au>Ezzedine, Mohamad</au><au>Rahimi, Hossein</au><au>Ghavamzadeh, Ardeshir</au><au>de Thé, Hugues</au><au>Hermine, Olivier</au><au>Mahmoudi, Mahmoud</au><au>Bazarbachi, Ali</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma</atitle><jtitle>Retrovirology</jtitle><addtitle>Retrovirology</addtitle><date>2013-08-20</date><risdate>2013</risdate><volume>10</volume><issue>1</issue><spage>91</spage><epage>91</epage><pages>91-91</pages><artnum>91</artnum><issn>1742-4690</issn><eissn>1742-4690</eissn><abstract>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/T(reg) 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 T(reg)/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.
The observed shift from a T(reg)/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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>23962110</pmid><doi>10.1186/1742-4690-10-91</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-1113-4472</orcidid><orcidid>https://orcid.org/0000-0002-7171-4997</orcidid><orcidid>https://orcid.org/0000-0002-1069-0477</orcidid><orcidid>https://orcid.org/0000-0003-2574-3874</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1742-4690 |
| ispartof | Retrovirology, 2013-08, Vol.10 (1), p.91-91, Article 91 |
| issn | 1742-4690 1742-4690 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3751834 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; SpringerNature Journals; PubMed Central Open Access; Springer Nature OA Free Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adult Aged Analysis Arsenic Arsenic Trioxide Arsenicals - administration & dosage Bacterial infections Blood donors Cytokines Cytokines - genetics Disease Dosage and administration Drug therapy Drug therapy, Combination Female Gene expression Gene Expression Profiling Health aspects HTLV-I Infections - drug therapy HTLV-I Infections - immunology Human health and pathology Human T-lymphotropic virus 1 Humans Immunologic Factors - administration & dosage Immunology Infections Infectious diseases Interferon Interferon-alpha - administration & dosage Interleukins Internal medicine Leukemia Leukemia-Lymphoma, Adult T-Cell - drug therapy Leukemia-Lymphoma, Adult T-Cell - immunology Life Sciences Lymphoma Lymphomas Male Middle Aged Oxides - administration & dosage Physiological aspects Prognosis Prospective Studies RNA Statistical analysis T cells Thermal cycling Treatment Outcome Viral infections Zidovudine Zidovudine - administration & dosage |
| title | The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T20%3A32%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20combination%20of%20arsenic,%20interferon-alpha,%20and%20zidovudine%20restores%20an%20%22immunocompetent-like%22%20cytokine%20expression%20profile%20in%20patients%20with%20adult%20T-cell%20leukemia%20lymphoma&rft.jtitle=Retrovirology&rft.au=Kchour,%20Ghada&rft.date=2013-08-20&rft.volume=10&rft.issue=1&rft.spage=91&rft.epage=91&rft.pages=91-91&rft.artnum=91&rft.issn=1742-4690&rft.eissn=1742-4690&rft_id=info:doi/10.1186/1742-4690-10-91&rft_dat=%3Cgale_pubme%3EA534690552%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1438899900&rft_id=info:pmid/23962110&rft_galeid=A534690552&rfr_iscdi=true |