{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:55:47Z","timestamp":1787068547309,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>L\u2010tryptophan (Trp) metabolism through the L\u2010kynurenine (Kyn) pathway contributes to immune escape in neoplasms, including bladder cancer (BC). Indoleamine 2,3\u2010dioxygenase\u20101 (IDO1) is a key enzyme, and its catabolites\u2014Kyn, 3\u2010hydroxykynurenine (3HK), and 3\u2010hydroxyanthranilate (3HAA)\u2014depend on other enzymes and play a crucial role in immunomodulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated the association between Kyn pathway enzyme expression and BC prognostic factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from 165\u2009\n                      <jats:sc>bc<\/jats:sc>\n                      patients in the GEO DataSets were analyzed, comparing staging, tumor grade, progression, and recurrence with the expression of IDO1, arylformamidase (AFMID), kynurenine\u2013oxoglutarate transaminase (KAT), kynureninase (KYNU), kynurenine 3\u2010monooxygenase (KMO), 3\u2010hydroxyanthranilate 3,4\u2010dioxygenase (HAAO), and aminocarboxymuconate\u2010semialdehyde decarboxylase (ACMSD). Predictive genes were further evaluated in RT4 (low\u2010grade, non\u2010invasive) and T24 (high\u2010grade, invasive) BC cells treated with IFN\u2010gamma and the IDO1 inhibitor INCB024360. Trp catabolites were quantified in the supernatant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Enzyme expression varied widely, especially for IDO1, AFMID, KAT, KMO, and KYNU. IDO1 correlated positively with KMO and negatively with KAT. High IDO1 and KMO levels were linked to advanced\u2010stage disease, while KAT and KYNU were associated with earlier stages and lower tumor grade. RT4 and T24 cells showed distinct basal enzyme expression, with T24 cells being more responsive to IFN\u2010gamma, increasing IDO1 and KYNU while decreasing KAT and KMO. These effects were inhibited by INCB024360. High Trp consumption increased Kyn and 3HAA but not 3HK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Kyn pathway enzyme expression varies with disease progression and may indicate immune activity by influencing tumor microenvironment catabolites. BC cell sensitivity to immune stimuli differs, potentially shaping distinct immune escape mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iju.70491","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:17:17Z","timestamp":1778149037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stage\u2010Dependent Changes in Kynurenine Pathway Enzyme Expression Suggest Immune\u2010Related Involvement in Bladder Cancer Progression"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4115-6095","authenticated-orcid":false,"given":"Douglas Edgard","family":"Lemes","sequence":"first","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine Universidade Nove de Julho (Uninove)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-2762","authenticated-orcid":false,"given":"Aline \u00c1urea de Souza","family":"Santos","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine Universidade Nove de Julho (Uninove)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-8546","authenticated-orcid":false,"given":"J\u00e9ssica Lopes","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine Universidade Nove de Julho (Uninove)  S\u00e3o Paulo SP 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Pinto","family":"Camacho","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine Universidade Nove de Julho (Uninove)  S\u00e3o Paulo SP Brazil"},{"name":"Thyroid Diseases Center, Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7012-7806","authenticated-orcid":false,"given":"Jos\u00e9","family":"Pontes\u2010Junior","sequence":"additional","affiliation":[{"name":"Urology Department, LIM\/55 \u2010 Laboratory of urology Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, Universidade de S\u00e3o Paulo, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo  S\u00e3o Paulo SP 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