{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:06:39Z","timestamp":1787799999142,"version":"build-2784847793"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Indoleamine 2,3\u2010dioxygenase (IDO) is an immunosuppressive tryptophan\u2010depleting enzyme expressed in nasopharyngeal carcinoma (NPC) tissue. However, IDO has not been reported in the peripheral blood of NPC patients. The aim of this study was to analyze, IDO1 and IDO2 messenger RNA (mRNA) expression, the kynurenine (Kyn) and tryptophan (Trp) plasma levels, their clinical values and their relationship with cytokine levels in NPC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated IDO1 and IDO2 mRNA expression in peripheral blood mononuclear cells (PBMC) by quantitative real\u2010time PCR, plasma Trp and Kyn levels by HPLC, and cytokine levels by ELISA in 75 NPC patients and 51 healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to controls, IDO1 mRNA expression was significantly upregulated and IDO2 mRNA expression was significantly downregulated in PBMC of patients. Also compared to controls, plasma Kyn levels and Kyn\/Trp ratio were significantly higher in patients. At the time of diagnosis, the plasma Kyn\/Trp ratio was associated with advanced cancer status and was an independent prognostic factor for worse disease\u2010specific survival. According to cancer stages, IDO1 mRNA expression was positively correlated with plasma Kyn\/Trp ratio in patients with earlier stages (I\u2013II\u2013III) but negatively correlated in patients with the late\u2010stage cancer (IV). Tumor necrosis factor\u2010\u03b1, interleukin (IL)\u20106 and IL\u201010 levels were significantly higher in patients compared to controls. Moreover, and despite treatment, patients simultaneously carrying high plasma Kyn\/Trp ratio and high plasma IL\u20106 and IL\u201010 levels at diagnosis died approximately 1 year after first diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Measuring blood IDO mRNA expression and Kyn\/Trp ratio at diagnosis could be a potential marker to evaluate NPC progression and predict survival outcome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.690","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T06:50:07Z","timestamp":1661842207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Indoleamine 2,3\u2010dioxygenase gene expression and kynurenine to tryptophan ratio correlation with nasopharyngeal carcinoma progression and survival"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6232-2484","authenticated-orcid":false,"given":"Sameh","family":"Souissi","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immuno\u2010Oncology, Faculty of Medicine of Monastir University of Monastir Monastir Tunisia"},{"name":"Higher Institute of Biotechnology of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randa","family":"Ghedira","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immuno\u2010Oncology, Faculty of Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosra","family":"Macherki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immuno\u2010Oncology, Faculty of Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahlem","family":"Ben\u2010Haj\u2010Ayed","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immuno\u2010Oncology, Faculty of Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sallouha","family":"Gabbouj","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immuno\u2010Oncology, Faculty of Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Remadi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immuno\u2010Oncology, Faculty of Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imen","family":"Sfar","sequence":"additional","affiliation":[{"name":"Research Laboratory in Immunology of Renal Transplantation and Immunopathology Tunis El Manar University Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohra","family":"Chadli","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Aouam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Hassine","sequence":"additional","affiliation":[{"name":"Department of Hematology Fattouma Bourguiba University Hospital Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noureddine","family":"Bouaouina","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immuno\u2010Oncology, Faculty of Medicine of Monastir University of Monastir Monastir Tunisia"},{"name":"Department of Cancerology and Radiotherapy Farhat Hached University Hospital Sousse Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelfattah","family":"Zakhama","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immuno\u2010Oncology, Faculty of Medicine of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4195-0091","authenticated-orcid":false,"given":"Elham","family":"Hassen","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immuno\u2010Oncology, Faculty of Medicine of Monastir University of Monastir Monastir Tunisia"},{"name":"Higher Institute of Biotechnology of Monastir University of Monastir Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30956-0"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2015.16.7.2653"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2014.02.006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.10.009"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.03.013"},{"issue":"6","key":"e_1_2_10_8_1","first-page":"3190","article-title":"An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells","volume":"185","author":"Mezrich JD","year":"2010","journal-title":"J Immunol Baltim Md 1950"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5380.1191"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2017.07.004"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2007.04.010"},{"issue":"3","key":"e_1_2_10_12_1","first-page":"1231","article-title":"The SOCS3\u2010independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells","volume":"192","author":"Trabanelli S","year":"2014","journal-title":"J Immunol Baltim Md 1950"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm934"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2015.11.012"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-92810-2_24"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019823"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2019.102288"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S301837"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020121"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000096906"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2008.06.014"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2009.05.001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.4161\/2162402X.2014.981457"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094403"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01243"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.4161\/2162402X.2014.982382"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-416"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03678-13"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0752-4"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-034785"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxt073"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2016.04.008"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820139.2012.676122"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-011-1066-1"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062284"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1637"},{"issue":"8","key":"e_1_2_10_37_1","first-page":"8389","article-title":"Tumor cells induced\u2010M2 macrophage favors accumulation of Treg in nasopharyngeal carcinoma","volume":"10","author":"Wang J","year":"2017","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073514"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172264"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1196"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-3026"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2272"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.78.9602"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0562-8"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-01847-4"}],"container-title":["Immunity, Inflammation and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.690","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/iid3.690","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.690","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T15:36:00Z","timestamp":1692459360000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/iid3.690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,29]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1002\/iid3.690"],"URL":"https:\/\/doi.org\/10.1002\/iid3.690","archive":["Portico"],"relation":{},"ISSN":["2050-4527","2050-4527"],"issn-type":[{"value":"2050-4527","type":"print"},{"value":"2050-4527","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,29]]},"assertion":[{"value":"2022-02-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e690"}}