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However, the potential value of plasma sEV in clinical prognosis prediction of triple\u2010negative breast cancer (TNBC) and their biological functions have not been well elucidated. In this study, we isolated sEV from non\u2010metastatic and metastatic TNBC plasma samples. We found that the expression of reticulin 4 (RTN4) in metastatic patients was significantly higher than that in non\u2010metastatic patients. At the same time, clinical data showed that RTN4 was associated with poor prognosis and advanced\u2010stage TNBC patients. Subsequently, in vivo and in vitro assays showed that compared to RTN4\n                    <jats:sup>Low<\/jats:sup>\n                    sEV, RTN4\n                    <jats:sup>high<\/jats:sup>\n                    sEV significantly promoted tumour cell migration, invasion, epithelial\u2010mesenchymal transition (EMT) and lung metastasis, and upregulated the expression of PD\u2010L1 in tumour tissues and inhibited CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration. Regarding mechanism research, we found that RTN4 within sEV drives tumour EMT and PD\u2010L1 expression by activating the NF\u2010\u03baB signalling pathway. Further, through the combined treatment experiment of anti\u2010PD\u20101 and anti\u2010RTN4, it was found that the combination of the two drugs was significantly superior to monotherapy in inhibiting tumour metastasis, EMT, and promoting CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration. Our results highlight the molecular mechanism of sEV protein RTN4 in tumour progression and immune system regulation, indicating that RTN4 targeting and anti\u2010PD\u20101 combined therapy have clinical potential. sEV protein RTN4 is a potential new prognostic marker for non\u2010invasive detection of TNBC and a new target for TNBC treatment.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70154","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T07:16:37Z","timestamp":1755674197000},"source":"Crossref","is-referenced-by-count":5,"title":["Targeting Reticulin 4 (RTN4) Within Small Extracellular Vesicles Combats Metastasis and Reinforces Immunotherapy in Triple\u2010Negative Breast Cancer"],"prefix":"10.1002","volume":"14","author":[{"given":"Han","family":"Wang","sequence":"first","affiliation":[{"name":"Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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