{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:51:48Z","timestamp":1790736708293,"version":"4.1.0"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"20","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"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":["81670687"],"award-info":[{"award-number":["81670687"]}],"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":["81970661"],"award-info":[{"award-number":["81970661"]}],"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":["81800672"],"award-info":[{"award-number":["81800672"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tai Shan Scholar Foundation","award":["ts201511092"],"award-info":[{"award-number":["ts201511092"]}]},{"name":"Primary Research and Development Plan of Shandong Province","award":["2019GSF108123"],"award-info":[{"award-number":["2019GSF108123"]}]},{"DOI":"10.13039\/100018904","name":"Beijing Xisike Clinical Oncology Research Foundation","doi-asserted-by":"publisher","award":["Y-2019AZQN-0557"],"award-info":[{"award-number":["Y-2019AZQN-0557"]}],"id":[{"id":"10.13039\/100018904","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303171"],"award-info":[{"award-number":["82303171"]}],"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":[[2024,5,14]]},"abstract":"<jats:p>\n                    The immune landscape of bladder cancer progression is not fully understood, and effective therapies are lacking in advanced bladder cancer. Here, we visualized that bladder cancer cells recruited neutrophils by secreting interleukin-8 (IL-8); in turn, neutrophils played dual functions in bladder cancer, including hepatocyte growth factor (HGF) release and CCL3\n                    <jats:sup>high<\/jats:sup>\n                    PD-L1\n                    <jats:sup>high<\/jats:sup>\n                    super-immunosuppressive subset formation. Mechanistically, c-Fos was identified as the mediator of HGF up-regulating IL-8 transcription in bladder cancer cells, which was central to the positive feedback of neutrophil recruitment. Clinically, compared with serum IL-8, urine IL-8 was a better biomarker for bladder cancer prognosis and clinical benefit of immune checkpoint blockade (ICB). Additionally, targeting neutrophils or hepatocyte growth factor receptor (MET) signaling combined with ICB inhibited bladder cancer progression and boosted the antitumor effect of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in mice. These findings reveal the mechanism by which tumor\u2013neutrophil cross talk orchestrates the bladder cancer microenvironment and provide combination strategies, which may have broad impacts on patients suffering from malignancies enriched with neutrophils.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2312855121","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T12:46:52Z","timestamp":1715086012000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":52,"title":["Tumor\u2013neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression"],"prefix":"10.1073","volume":"121","author":[{"given":"Weiqiang","family":"Jing","sequence":"first","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Qilu Hospital Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1274-1418","authenticated-orcid":false,"given":"Zhiwei","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Immunology, Shandong Provincial Key Laboratory of Infection &amp; Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, Shandong Provincial Key Laboratory of Infection &amp; Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8060-4486","authenticated-orcid":false,"given":"Shuyan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Immunology, Shandong Provincial Key Laboratory of Infection &amp; Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wushan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Jinan Maternity and Child Care Hospital Shandong First Medical University, Jinan, Shandong Province 250000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Han","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianzeng","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Urology and State Key Laboratory of Molecular Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 10021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Immunology, Shandong Provincial Key Laboratory of Infection &amp; Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouzhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benkang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21631"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.17598"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-3842"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00571-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0915-y"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.12.012"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aag1711"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao4227"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008112117"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv159"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal5081"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2013.218"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2022.155828"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0856-x"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0860-1"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.03.004"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.02.042"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2019.09.023"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-021-03000-8"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-1319"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1115"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2463"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.001"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310344"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.047"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.01.012"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01863-w"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01503-1"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.01.252"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1330"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00152-5"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.421"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14407"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.09.012"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010247"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100866"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-0988"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0306-5"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-36667-4_2"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25501"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3203"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx190"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83871"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613683"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30616-2"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0136-1"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-3614"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.016"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.52"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0281-y"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.03.012"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.06.017"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04651"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(02)00045-X"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.03.012"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0235-4"},{"key":"e_1_3_4_57_2","doi-asserted-by":"crossref","unstructured":"W.Q. Jing RNA-seq analysis for Tumor-neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression. Genome Sequence Archive (GSA). https:\/\/ngdc.cncb.ac.cn\/gsa\/browse\/CRA015417. Deposited 18 March 2024.","DOI":"10.1073\/pnas.2312855121"},{"key":"e_1_3_4_58_2","unstructured":"W.Q. Jing scRNA-seq analysis of MACS-sorted Ly6G+ neutrophils from mouse bladder tumors. Genome Sequence Archive (GSA). https:\/\/ngdc.cncb.ac.cn\/gsa\/browse\/CRA015418. Deposited 17 March 2024."},{"key":"e_1_3_4_59_2","unstructured":"B.K. Shi CHIP-seq analysis for Tumor-neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression. Genome Sequence Archive for Human (GSA-human). https:\/\/ngdc.cncb.ac.cn\/gsa-human\/browse\/HRA006957. Deposited 20 March 2024."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2312855121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T01:17:01Z","timestamp":1731892621000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2312855121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,7]]},"references-count":59,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2024,5,14]]}},"alternative-id":["10.1073\/pnas.2312855121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2312855121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,7]]},"assertion":[{"value":"2023-07-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2312855121"}}