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This study integrates single\u2010nucleus RNA sequencing, spatial transcriptomics, and multiplex immunohistochemistry to elucidate the TME and mechanisms of relapse in NSMP EC. The results showed reduced immune infiltration and increased immune\u2010suppressive cells, including SPP1+ macrophages and regulatory T cells (Tregs) in NSMP EC. More epithelial cell clusters with high stemness scores are observed in primary NSMP EC tumors collected before recurrence. In NSMP EC, tip endothelial cells and MMP11+ LEF1+ cancer\u2010associated fibroblasts (CAFs) are linked with angiogenesis and epithelial\u2010mesenchymal transition, and CD4+ T cells remain in a stress\u2010response state and are functionally impaired. Interestingly, a subset of tumor\u2010associated macrophages (TAMs) characterized by SPP1 expression is discovered, which may remodel the tumor microenvironment by potentially promoting CD4+ T cells stress and maintaining epithelial cells stemness through SPP1\u2010CD44, thereby potentially contributing to the proliferation and migration of tumor cells, which has verified by in vitro experiments. This study advances the mechanistic understanding of recurrence\u2010related TME and provides a foundation for the development of personalized treatments for NSMP EC patients.<\/jats:p>","DOI":"10.1002\/advs.78332","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:20:12Z","timestamp":1792556412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Characteristics of Tumor Microenvironment by the Single Cell Profile in Endometrial Cancer of no Specific Molecular Profile (NSMP) Subtype"],"prefix":"10.1002","author":[{"given":"Xinhui","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Gynecologic Oncology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology Shanghai Medical College Fudan University  Shanghai 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