{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:03:43Z","timestamp":1791237823152,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203769"],"award-info":[{"award-number":["82203769"]}],"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":["82072877"],"award-info":[{"award-number":["82072877"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82203769"],"award-info":[{"award-number":["82203769"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82072877"],"award-info":[{"award-number":["82072877"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High-grade serous ovarian carcinoma (HGSOC) shows limited benefit from immune checkpoint blockade, partly because stromal barriers impair antitumor immunity. We developed a cancer-associated fibroblast (CAF)-associated mitochondrial metabolic and matrix-remodeling signature, termed CMMS, to characterize this immune-suppressive stromal state. CMMS integrated contractile\/myCAF, extracellular matrix (ECM), and mitochondrial metabolic genes. Its clinical, metabolic, and immune relevance was evaluated in TCGA-HGSOC, independent GEO cohorts, single-cell RNA-seq datasets, and an anti-PD-L1-treated cohort, followed by cell\u2013cell communication and experimental validation. LASSO-weighted CMMS stratified overall survival, with high CMMS indicating poorer prognosis. CMMS-high tumors exhibited ECM\/TGF\u03b2 activation; associations with COL1A1, POSTN, and LOX; and a hypoxia-dominant metabolic phenotype. Mediation analysis suggested that hypoxia largely linked CMMS to glycolytic remodeling. Immune profiling revealed stromal-rich immune exclusion, checkpoint activation, and exhaustion-prone T-cell dysfunction. Single-cell analysis localized CMMS mainly to myCAF-like ECM-remodeling CAFs. In validation datasets, CMMS-high CAFs were associated with reduced CD8 abundance, increased CD8 exhaustion, and stronger matrix- and chemokine-related communication with T cells. Experiments further supported a link between TGF\u03b2-related fibroblast activation, ECM-remodeling features, and impaired CD8+ T-cell effector function. Overall, CMMS defines a CAF-enriched fibrotic\u2013hypoxic stromal program associated with immune exclusion-related features, exhaustion-prone T-cell dysfunction, and poor outcome in HGSOC.<\/jats:p>","DOI":"10.3390\/ijms27136092","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:27:31Z","timestamp":1783531651000},"page":"6092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A CAF-Associated Stromal Remodeling Signature Links Immune Exclusion to Exhaustion-Prone CD8+ T-Cell Dysfunction in High-Grade Serous Ovarian Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Yang","family":"Bai","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Reproduction and Development, Shanghai 200433, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifang","family":"Chen","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Reproduction and Development, Shanghai 200433, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lu","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"},{"name":"Shanghai Key Laboratory of Reproduction and Development, Shanghai 200433, China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"972","DOI":"10.6004\/jnccn.2022.0047","article-title":"NCCN Guidelines(R) Insights: Ovarian Cancer, Version 3.2022","volume":"20","author":"Armstrong","year":"2022","journal-title":"J. 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