{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:29:10Z","timestamp":1787005750790,"version":"build-2736575974"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"15","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473955"],"award-info":[{"award-number":["82473955"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173842"],"award-info":[{"award-number":["82173842"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,4,14]]},"abstract":"<jats:p>\n                    Bladder cancer remains a significant therapeutic challenge due to its marked heterogeneity and capacity for immune evasion. Here, we employ spatial metabolomics and spatial transcriptomics to systematically characterize and visualize the metabolic and transcriptional landscapes of bladder cancer. Our findings identify distinct metabolic and transcriptional profiles across different tumor regions, highlighting heterogeneity and immune-associated metabolic reprogramming in BLCA. Further investigation identifies zinc finger protein 36 (ZFP36) as a potential immunotherapeutic target. Utilizing\n                    <jats:italic toggle=\"yes\">Zfp36<\/jats:italic>\n                    whole-body knockout and T cell\u2013specific\n                    <jats:italic toggle=\"yes\">Zfp36<\/jats:italic>\n                    conditional knockout mice, we validated that\n                    <jats:italic toggle=\"yes\">Zfp36<\/jats:italic>\n                    knockout decreases the activation threshold for T cells and increases T cell infiltration in tumors. Moreover, we found that elevated ZFP36 expression is dramatically linked to worse patient outcomes. Mechanistically, ZFP36 facilitates mRNA degradation of key immune regulators, including\n                    <jats:italic toggle=\"yes\">C1QBP<\/jats:italic>\n                    , thereby inhibiting T cell activation and cytotoxicity. Notably, combining\n                    <jats:italic toggle=\"yes\">Zfp36<\/jats:italic>\n                    knockout with anti-PD-1 therapy produced synergistic antitumor effects, suggesting that ZFP36 inhibition could be a promising therapeutic strategy. This integrated multiomics approach collectively uncovers immune-metabolic regulatory pathways in BLCA and points to critical molecular targets for immunotherapy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2505125123","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T17:04:44Z","timestamp":1775667884000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Spatial multiomics profiling reveals ZFP36-mediated immunometabolic reprogramming in bladder cancer"],"prefix":"10.1073","volume":"123","author":[{"given":"Fangdie","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Urology, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Fudan Institute of Urology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuedan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University","place":["Nanjing, Jiangsu Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Fudan Institute of Urology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0568-0645","authenticated-orcid":false,"given":"Lei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell and Cancer Biology, University of Massachusetts Chan Medical School","place":["Worcester"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Fudan Institute of Urology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University","place":["Nanjing, Jiangsu Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5029-9190","authenticated-orcid":false,"given":"Hang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Wenzhou Medical University","place":["Wenzhou City, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Huashan Hospital, Fudan University","place":["Shanghai, China"]},{"name":"Fudan Institute of Urology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2183-4974","authenticated-orcid":false,"given":"Lufeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University","place":["Nanjing, Jiangsu Province, 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Zheng F. Ye X. Han Data from \u201cUnveiling immune metabolic mechanisms in bladder cancer: Spatial profiling identifies ZFP36 as a therapeutic target.\u201d NCBI. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE285715. Deposited 9 July 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2505125123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T17:05:55Z","timestamp":1775667955000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2505125123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":54,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2026,4,14]]}},"alternative-id":["10.1073\/pnas.2505125123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2505125123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]},"assertion":[{"value":"2025-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2505125123"}}