ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Exosomal CMTM4 Induces Immunosuppressive Macrophages to Promote Ovarian Cancer Progression and Attenuate Anti-PD-1 Immunotherapy.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Applications of Exosomes in Female Medicine: A Systematic Review of Molecular Biology, Diagnostic and Therapeutic Perspectives.International journal of molecular sciences · 2026Pooled it
- Multi-omics analysis identifies CKLF as a promoter for HCC progression by regulating the AKT, ERK pathways, and infiltrating immune cells.Translational oncology · 2026Article
- Potential Role of Exosomes in the Pathogenesis, Diagnosis, and Treatment of Ovarian Cancer.Cancers · 2026Review
- Article
- Advances in understanding exosome-mediated regulation of macrophage function.Frontiers in immunology · 2026Review
- Research progress ofFrontiers in immunology · 2026Review
- Macrophage polarization in gynecologic malignancies: key signaling pathways and clinical perspectives.Frontiers in immunology · 2026Review
- Identification of LILRB4 as a regulator of M2c macrophages and a potential immunotherapeutic target in ovarian cancer.Frontiers in immunology · 2026Article
- Glycolysis and T cell-associated gene signature predicts prognosis and therapeutic responses in pancreatic cancer.Frontiers in immunology · 2026Article
- Necroptosis-senescence crosstalk in tubulointerstitial fibrosis: the mtDNA-cGAS-STING-PFKFB3 axis as a metabolic bridge.Frontiers in medicine · 2026Review
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Urine-Derived CD105-Positive Exosome Promotes Macrophage M1 Polarization Through the TGF-β1/Smad3 Signaling Axis To Exacerbate Lupus Nephritis.Inflammation · 2025Article
- Advances in the use of exosomes for the diagnosis and treatment of ovarian cancer.World journal of surgical oncology · 2025Review
- Engineered iron oxide nanoplatforms: reprogramming immunosuppressive niches for precision cancer theranostics.Molecular cancer · 2025Review
- Graph-based deep learning for integrating single-cell and bulk transcriptomic data to identify clinical cancer subtypes.Briefings in bioinformatics · 2025Article
- Exosomal CMTM4 Induces Immunosuppressive Macrophages to Promote Ovarian Cancer Progression and Attenuate Anti-PD-1 Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Macrophages and neutrophils in ovarian cancer microenvironment.Frontiers in immunology · 2025Review
- Burden and trends of ovarian and uterine cancer due to high body mass index from 1990 to 2021: an age-period-cohort study based on the GBD 2021, and projections through 2036.Frontiers in oncology · 2025Article
- Oncogenic CMTM6 drives M2a macrophages formation and fuels cervical cancer progression.Frontiers in immunology · 2025Article
- Clinicopathologic and Molecular Characterization of Colorectal Cancer in Patients Aged ≥80 years.Clinical interventions in aging · 2025Article
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Authors and funding
13 authors.
Funding
Abstract
Exosomes shape the tumor microenvironment (TME) by modulating tumor-associated macrophages (TAMs) and promoting ovarian cancer (OC) progression. This study reveals that exosomal CKLF Like MARVEL Transmembrane Domain Containing 4 (CMTM4) enhances OC malignancy and orchestrates immune evasion. Excessive macrophage infiltration in the TME, particularly in the presence of CMTM4, is strongly associated with poor prognosis. Within the TME, exosomal CMTM4 is actively internalized by macrophages, promoting M2 polarization and subsequently initiating immunosuppressive signaling. Exosomal CMTM4 activates the NF-κB pathway in TAMs, suppressing immune function through enhanced secretion of cytokines, including TGF-β1 and CXCL12, while simultaneously upregulating intercellular adhesion molecule-1 (ICAM1) expression to further promote M2 polarization and facilitate cancer metastasis. Depletion of CMTM4 increases sensitivity to anti-PD-1 therapy by reversing immunosuppression. Notably, eltrombopag is identified as a CMTM4 inhibitor that attenuates OC progression in vivo and modulates the tumor immune microenvironment, synergizing with PD-1 blockade immunotherapy to enhance therapeutic efficacy. The exosomal CMTM4-ICAM1-CD206 axis exacerbates disease risk in patients with OC. Collectively, the study highlights the critical role of tumor-derived exosomal CMTM4 in immune suppression, emphasizing its potential as both a prognostic biomarker and a therapeutic target in OC immunotherapy.
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