{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:06:17Z","timestamp":1790244377888,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"53","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373254"],"award-info":[{"award-number":["82373254"]}],"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":["82560566"],"award-info":[{"award-number":["82560566"]}],"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":["82403416"],"award-info":[{"award-number":["82403416"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intratumoral microbiota\u2010related metabolites are emerging regulators of tumor immunity, yet their therapeutic potential remains largely unexplored. Here, indole\u20103\u2010pyruvic acid (I3P), a Lactobacillus\u2010associated tryptophan metabolite, is identified as a molecule associated with immunotherapy response in bladder cancer. Mechanistically, I3P suppresses macrophages ferroptosis and sustains CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u00a0activity through an AHR\u2013NF\u2010\u03baB\u2013SLC7A11 signaling axis that maintains macrophages redox homeostasis. Disruption of AHR or NF\u2010\u03baB signaling abolishes these effects. Notably, liposomal delivery of I3P facilitates efficient targeting of tumor\u2010associated macrophages and enhances immunotherapy response without apparent toxicity. Together, these findings identify I3P as an immunoregulatory metabolite that potentiates anti\u2010tumor immunity and support nanoparticle\u2010mediated delivery as a promising strategy for immunotherapy sensitization in bladder cancer.\n                  <\/jats:p>","DOI":"10.1002\/advs.76319","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:32:16Z","timestamp":1783009936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted Delivery of Indole\u20103\u2010Pyruvic Acid Suppresses Macrophage Ferroptosis to Enhance CD8\n                    <sup>+<\/sup>\n                    T Cell\u2010Mediated Immunotherapy Response in Bladder Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Jianwen","family":"Lao","sequence":"first","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhao","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Urology Yan'an Hospital Kunming Medical University  Kunming P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Urology Yan'an Hospital Kunming Medical University  Kunming P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daqin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peicong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology Yan'an Hospital Kunming Medical University  Kunming P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Yan'an Hospital Kunming Medical University  Kunming P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Urology Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou P. R. China"},{"name":"Guangdong Provincial Clinical Research Center For Urological Diseases  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1514296"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.02.032"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.17598"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010019\u20100116\u2010x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy495"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-023-00594-2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201000974\u20104"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201001698\u20102"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.12.010"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2025.07.005"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003727\u20105"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.12.013"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.041"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.01.006"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010022\u201001267\u20102"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010022\u201000520\u20105"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.08.027"},{"key":"e_1_2_10_20_1","article-title":"Gut Microbiota\u2010Butyrate\u2010PPAR\u03b3 Axis Modulates Adipose Regulatory T Cell Population","volume":"12","author":"Chen B.","year":"2025","journal-title":"Advancement of Science"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2026.03.024"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2023.06.005"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.08.009"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.08.003"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-026-10193-4"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010024\u201002047\u2010w"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.03.011"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008440\u20107"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.003"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2022.02.023"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217115"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.044"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000003189"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007623\u20106"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201046776\u2010w"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.04.007"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.10.010"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics9020012"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2015.06.006"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.12.044"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.07.002"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.2191"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.05.018"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2467235"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010023\u201001314\u20106"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010025\u201001888\u20102"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.08.016"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2026.01.020"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.10.007"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76319","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.76319","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76319","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:16:58Z","timestamp":1790241418000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.76319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":48,"journal-issue":{"issue":"53","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/advs.76319"],"URL":"https:\/\/doi.org\/10.1002\/advs.76319","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"assertion":[{"value":"2026-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e76319"}}