{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:22:42Z","timestamp":1782519762149,"version":"3.54.5"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"1","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772755"],"award-info":[{"award-number":["81772755"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772755"],"award-info":[{"award-number":["81772755"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Commun"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Indoleamine 2,3\u2010dioxygenase 1 (IDO1) and tryptophan (Trp) catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penile squamous cell carcinoma (PSCC) and explored their clinical significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn) were examined in 114 PSCC patients by immunohistonchemistry and solid\u2010phase extraction\u2010liquid chromatography\u2010tandem mass spectrometry. The survival was analyzed using Kaplan\u2010Meier method and the log\u2010rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were defined by principal component analysis. The correlativity was assessed by Pearson's correlation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The expression level of IDO1 in PSCC cells was positively correlated with serum Kyn concentration and Kyn\/Trp radio (KTR; both\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) but negatively correlated with serum Trp concentration (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a00.001). Additionally, IDO1 up\u2010regulation in cancer cells and the increase of serum KTR were significantly associated with advanced N stage (both\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) and high pathologic grade (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a00.008 and 0.032, respectively). High expression level of IDO1 in cancer cells and serum KTR were associated with short disease\u2010specific survival (both\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). However, besides N stage (hazard radio [HR], 6.926; 95% confidence interval [CI], 2.458\u201019.068;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) and pathologic grade (HR, 2.194; 95% CI, 1.021\u20104.529;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a00.038), only serum KTR (HR, 2.780; 95% CI, 1.066\u20107.215;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0=\u00a00.036) was an independent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon\u2010\u03b3 (IFN\u03b3,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) and immunosuppressive markers (programmed cell death protein 1, cytotoxic T\u2010lymphocyte\u2010associated protein 4 and programmed death\u2010ligand 1 and 2; all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05), and the infiltration of immune cells (including cytotoxic T lymphocytes, regulatory T lymphocytes, tumor\u2010associated macrophages, and myeloid\u2010derived suppressor cells; all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) in PSCC tissues. Furthermore, the expression of IDO1 was induced by IFN\u03b3 in a dose\u2010dependent manner in PSCC cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">IFN\u03b3\u2010induced IDO1 plays a crucial role in immunoediting and immunosuppression in PSCC. Additionally, serum KTR, an indicator of IDO1 catabolic activity, can be utilized as an independent prognostic factor for PSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cac2.12001","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T05:22:19Z","timestamp":1583212939000},"page":"3-15","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Up\u2010regulation of indoleamine 2,3\u2010dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients"],"prefix":"10.34133","volume":"40","author":[{"given":"Qiang\u2010hua","family":"Zhou","sequence":"first","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Han","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010bin","family":"Lu","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang\u2010bo","family":"Huang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang\u2010zhong","family":"Deng","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zai\u2010shang","family":"Li","sequence":"additional","affiliation":[{"name":"Jinan\u00a0University","place":["Guangdong, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie\u2010ping","family":"Chen","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Yao","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010ke","family":"Qin","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo\u2010wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University Cancer Center","place":["Guangzhou, P. R. 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Pathophysiological basis of human papillomavirus in penile cancer: Key to prevention and delivery of more effective therapies. CA Cancer J Clin. 2016;66((6)):481\u201395. https:\/\/doi.org\/10.3322\/caac.21354.","journal-title":"CA Cancer J Clin"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.3389\/fimmu.2018.01253","article-title":"The Prognostic Value of Immune Factors in the Tumor Microenvironment of Penile Squamous Cell Carcinoma","volume":"9","author":"Ottenhof SR","year":"2018","unstructured":"Ottenhof SR, Djajadiningrat RS, Thygesen HH, Jakobs PJ, Jozwiak K, Heeren AM et\u00a0al. The Prognostic Value of Immune Factors in the Tumor Microenvironment of Penile Squamous Cell Carcinoma. 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