{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:06:04Z","timestamp":1793833564258,"version":"4.6.1"},"reference-count":33,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["(U21A20375)"],"award-info":[{"award-number":["(U21A20375)"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,22]]},"abstract":"<jats:p>Bladder cancer (BCa) mortality is mainly driven by metastatic dissemination and an immunosuppressive tumor microenvironment. Here, we identify ELN (tropoelastin), an extracellular matrix protein abundantly secreted by cancer-associated fibroblasts (CAFs), as a critical determinant of these processes and a marker of poor prognosis. ELN promotes epithelial-mesenchymal transition (EMT), facilitates lymphatic spread, and induces immune dysfunction characterized by macrophage polarization toward an M2 phenotype and T cell exhaustion. Mechanistically, ELN functions as a binding partner of TGF-\u03b2 receptor 2 (TGFBR2), thereby triggering SMAD2\/3-dependent TGF-\u03b21 secretion and establishing a feed forward signaling loop. This ELN\/TGFBR2\/TGF-\u03b21 axis amplifies metastatic capacity and immunosuppressive signaling, ultimately accelerating disease progression and diminishing responsiveness to immune checkpoint blockade. Functional studies in BCa organoids and murine models demonstrated that pharmacologic blockade of the ELN-TGFBR2 interaction effectively suppressed tumor metastasis and restored antitumor immunity. Collectively, our findings establish ELN as a CAF-derived driver of metastasis and immune evasion in BCa. Targeting the ELN-TGFBR2 interaction offers a promising therapeutic strategy to limit metastatic progression and enhance the efficacy of immunotherapy in this lethal disease.<\/jats:p>","DOI":"10.1172\/jci.insight.194700","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T18:00:52Z","timestamp":1779386452000},"source":"Crossref","is-referenced-by-count":2,"title":["ELN orchestrates prometastatic and immunosuppressive niche in bladder cancer via TGFB1 autocrine signaling"],"prefix":"10.1172","volume":"11","author":[{"given":"Wentao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China."},{"name":"Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei, China."},{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province and"},{"name":"Innovation and Entrepreneurship Laboratory 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