{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:23Z","timestamp":1792787303790,"version":"4.5.0"},"reference-count":62,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"unspecified","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007279","name":"Shanghai Municipal Health Bureau","doi-asserted-by":"publisher","award":["2020CXJQ03"],"award-info":[{"award-number":["2020CXJQ03"]}],"id":[{"id":"10.13039\/501100007279","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172741"],"award-info":[{"award-number":["82172741"]}],"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":["82473192"],"award-info":[{"award-number":["82473192"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Innovation Project of Shanghai Education Committee","award":["2021-01-07-00-07-E00080"],"award-info":[{"award-number":["2021-01-07-00-07-E00080"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,11,3]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have transformed the treatment strategy for bladder cancer (BLCA), but primary resistance still occurs in most patients. Recent evidence suggests that neutrophil extracellular traps (NETs) play a key role in cancer therapy resistance, but their specific role in BLCA remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An integrated analysis of multiple clinical cohorts receiving ICIs was performed to explore the link between NETs and patient outcomes. Immunofluorescence staining, in vitro co-culture system, scanning electron microscopy, and mouse lung metastasis model were used to evaluate the biological effects of NETs. Proteomics and single-cell transcriptomics analysis were further applied to elucidate the molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinically, NETs abnormally accumulated in BLCA and promoted tumor metastasis and immunotherapy resistance in mice. Mechanistically, NETs upregulated the anti-phagocytic checkpoint STC1 in tumor cells through the TLR2-MAPK-FosL1 axis. Notably, STC1 inhibited antigen presentation by sequestering calreticulin, while its secreted form enhances NET formation, forming a self-reinforcing feedback loop. In addition, secreted STC1 impaired differentiation of CD14\n                      <jats:sup>+<\/jats:sup>\n                      precursors into mature dendritic cells, further exacerbating immune suppression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study revealed the critical role of the NETs-STC1 feedback loop in BLCA immunoresistance. Targeting this axis could simultaneously enhance efficacy and safety of immunotherapy, providing a novel translational strategy for overcoming resistance in clinical settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012736","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T20:35:20Z","timestamp":1764362120000},"page":"e012736","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Neutrophil extracellular traps\u2013STC1 positive feedback loop promotes immune evasion and metastasis in bladder cancer"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0879-0291","authenticated-orcid":false,"given":"Tingting","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Fudan University, Shanghai, 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