{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:44:26Z","timestamp":1790804666173,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T00:00:00Z","timestamp":1565740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["CNPQ 134385\/2016-0"],"award-info":[{"award-number":["CNPQ 134385\/2016-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2012\/09746-2"],"award-info":[{"award-number":["2012\/09746-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/04926-6"],"award-info":[{"award-number":["2017\/04926-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Procad 88881.068413\/2014-01"],"award-info":[{"award-number":["Procad 88881.068413\/2014-01"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Human papillomavirus (HPV) infection is the central factor for cervical cancer, whereas epithelial immune mechanisms contribute to the progression of HPV infection and its associated lesions. The authors evaluated the expression of indoleamine 2,3\u2010dioxygenase (IDO) and tryptophan 2,3\u2010dioxygenase (TDO) in cervicovaginal samples from women with normal cervical epithelium or with different degrees of squamous intraepithelial lesions (SILs) and cervical cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IDO expression was analyzed by immunocytochemistry in liquid\u2010based cytology samples from 165 women, of whom 42 had cervical changes subclassified as low\u2010grade SIL (n\u00a0=\u00a06), high\u2010grade SIL (n\u00a0=\u00a030), or squamous cell carcinoma (SCC) (n\u00a0=\u00a06), and 123 had negative Papanicolaou smears. IDO and TDO expression also were analyzed by immunohistochemistry, and HPV and other genital pathogens were evaluated by polymerase chain reaction analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Low IDO expression was observed in normal cervical epithelium irrespective of HPV status. Increased numbers of IDO\u2010positive squamous cells and IDO\u2010positive leukocytes were observed in women with SIL or SCC. TDO expression was detected in leukocytes infiltrating the stroma around intraepithelial or invasive cervical lesions. Higher IDO levels were detected in organotypic epithelial cultures established from keratinocytes transduced with the HPV16 E6\/E7 oncoproteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The upregulation of IDO expression in leukocytes and squamous cells in HPV\u2010associated SIL and SCC suggests that immunosuppressive mechanisms involving tryptophan metabolism may have a role in cervical carcinogenesis. Although previous studies have suggested the role of IDO in HPV pathogenesis, this is the first evidence of TDO involvement in the process. Furthermore, the current data emphasize the role of leukocytes, especially neutrophil\u2010like cells, as an IDO source.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22172","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T15:19:57Z","timestamp":1565795997000},"page":"586-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Indoleamine 2,3\u2010dioxygenase and tryptophan 2,3\u2010dioxygenase expression in HPV infection, SILs, and cervical cancer"],"prefix":"10.1002","volume":"127","author":[{"given":"Paloma Almeida","family":"Venancio","sequence":"first","affiliation":[{"name":"Department of Clinical Analysis and Toxicology, School of Pharmaceutical Sciences University of Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia Edilaine Lopes","family":"Consolaro","sequence":"additional","affiliation":[{"name":"Clinical Cytology Laboratory State University of Maringa Maringa Parana Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie Fran\u00e7oise","family":"Derchain","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medical Sciences State University of Campinas Campinas Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Boccardo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences University of Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa Lina","family":"Villa","sequence":"additional","affiliation":[{"name":"Department of Radiology and Oncology, Faculty of Medicine University of Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvya Stuchi","family":"Maria\u2010Engler","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Toxicology, School of Pharmaceutical Sciences University of Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Campa","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Toxicology, School of Pharmaceutical Sciences University of Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3660-3826","authenticated-orcid":false,"given":"Michelle Garcia","family":"Discacciati","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Toxicology, School of Pharmaceutical Sciences University of Sao Paulo Sao Paulo Brazil"},{"name":"Department of Obstetrics and Gynecology, School of Medical Sciences State University of Campinas Campinas Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1020-49891999000900001"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2004.12.006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/emph\/eov003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir717"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31027"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09079-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pvr.2017.08.002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/GCO.0b013e32831a9890"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.10.001"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00384"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jons.2017.04.001"},{"key":"e_1_2_8_14_1","first-page":"673","article-title":"Cancer immunotherapy by targeting IDO1\/TDO and their downstream effectors","volume":"5","author":"Platten M","year":"2014","journal-title":"Front Immunol"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.222"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2016.04.008"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2008.33"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.4161\/2162402X.2014.981457"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2010.02.028"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000492849"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568009615666151030102250"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.01.011"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-2285"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/8169724"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0420"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13550-015-0136-9"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113873109"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-15-0420"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/LGT.0000000000000115"},{"key":"e_1_2_8_30_1","volume-title":"WHO Classification of Tumours of Female Reproductive Organs","author":"Kurman RJ","year":"2014"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0315"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.29.2.297-301.1991"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8794-1-29"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-14-0137"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753425913496442"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344406"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2009.953604"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.01.002"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431X20154524"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004651"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis280"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201449"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2013.06.003"},{"key":"e_1_2_8_44_1","article-title":"Role of tumor\u2010infiltrating lymphocytes in patients with solid tumors: can a drop dig a stone [published online February 1, 2018]?","author":"Badalamenti G","journal-title":"Cell Immunol"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700389"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2008.03.004"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.06.017"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/835956"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12150"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2016.03.018"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18217"},{"key":"e_1_2_8_52_1","first-page":"9507","article-title":"Circulating and tumor\u2010infiltrating myeloid\u2010derived suppressor cells in cervical carcinoma patients","volume":"15","author":"Wu L","year":"2018","journal-title":"Oncol Lett"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.4161\/2162402X.2014.984539"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm934"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-008-0513-6"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2007.00470.x"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/8.4.385"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.4161\/21624011.2014.968480"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10491"}],"container-title":["Cancer Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.22172","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncy.22172","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.22172","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T13:22:04Z","timestamp":1760275324000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncy.22172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,14]]},"references-count":58,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1002\/cncy.22172"],"URL":"https:\/\/doi.org\/10.1002\/cncy.22172","archive":["Portico"],"relation":{},"ISSN":["1934-662X","1934-6638"],"issn-type":[{"value":"1934-662X","type":"print"},{"value":"1934-6638","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,14]]},"assertion":[{"value":"2019-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}