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This study aimed to identify tumor microenvironment (TME) traits that predispose to RT-promoted DM and provide mechanistic insights for potential therapeutic intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed NanoString analysis on tumor samples from urothelial cancer patients to compare the TME profiles of those with and without RT-promoted DM. To complement clinical findings, we conducted RNA sequencing (RNAseq) of murine bladder cancer cell lines, MB49 (with RT-promoted DM) and MBT2 (without), followed by in vivo ectopic tumor modeling, flow cytometry of immune cell infiltrates, and cytokine array profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NanoString analysis revealed a significant enrichment of C-X-C motif receptor 2 (CXCR2)-expressing neutrophils in the TME of patients with RT-promoted DM. These tumors also exhibited nuclear factor kappa B (NF\u03baB) activation and increased secretion of neutrophil-recruiting chemokines. RNAseq and cytokine profiling identified CD14 expression in tumor cells as a key upstream regulator of neutrophilic TME via NF\u03baB signaling. The use of antagonists to block neutrophils and inhibit CD14 expression in cancer cells, which reduces the secretion of neutrophil-recruiting chemokines, effectively mitigated RT-promoted DM in both the MB49 and LLC mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CD14 expression in tumor cells plays a pivotal role in shaping a neutrophil-enriched TME, which increases the susceptibility to RT-promoted DM. CD14 represents a potential predictive biomarker and therapeutic target for mitigating this adverse outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-025-01201-2","type":"journal-article","created":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T07:53:57Z","timestamp":1767513237000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["High-CD14-expressing urothelial cancer cells foster a neutrophil-rich tumor microenvironment that increases the risk of radiation-promoted distant metastasis"],"prefix":"10.1186","volume":"33","author":[{"given":"Yun","family":"Chiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chieh","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Chieh","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Jen","family":"Hsueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Yuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Hsin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong-Shiau","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Chieh","family":"Chueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier Cheng-Hong","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason Chia-Hsien","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"issue":"16","key":"1201_CR1","doi-asserted-by":"publisher","first-page":"2999","DOI":"10.1007\/s00018-016-2210-5","volume":"73","author":"M Vilalta","year":"2016","unstructured":"Vilalta M, Rafat M, Graves EE. 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