{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:02:03Z","timestamp":1789732923113,"version":"4.0.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Aims and objectives<\/jats:title>\n                    <jats:p>High-grade serous ovarian cancer (HGSOC) ascites represents a highly immunosuppressive tumour microenvironment characterized by complex stromal\u2013immune interactions. In this study, we aimed to delineate the cellular communication networks shaping immune dysfunction within HGSOC ascites, identify key regulatory signalling pathways, characterize the fibroblast\u2013macrophage axis at single-cell resolution, and evaluate the therapeutic potential of IL-10 blockade in reversing macrophage-mediated immunosuppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-cell RNA sequencing data of eight ascites samples from six HGSOC patients (GSE146026) were analysed using Seurat for clustering and differential expression, followed by CellChat to infer ligand\u2013receptor communication. Sub-clustering defined inflammatory CAFs (iCAF), myofibroblast CAFs (mCAF), and macrophage subtypes (M1\/M2). GO\/KEGG enrichment assessed functional pathways. Multiplex immunofluorescence validated spatial interactions of IL10+ iCAF and IL10RA+ macrophages in patient tissues. An immune-humanized patient-derived xenograft (PDX) mouse model was established to evaluate the therapeutic effect of IL-10 blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Single-cell transcriptomic analysis of HGSOC ascites revealed macrophages and cancer-associated fibroblasts as dominant cell populations within the tumour microenvironment. Cell\u2013cell communication analysis identified IL-10\u2013IL-10RA signalling as a prominent interaction pathway linking inflammatory CAFs (iCAFs) with M2-like macrophages. iCAFs displayed elevated IL-10 expression, while M2 macrophages showed increased IL-10RA\/IL-10RB expression and were associated with exhausted immune states. Multiplex immunofluorescence confirmed spatial proximity between IL-10\n                      <jats:sup>+<\/jats:sup>\n                      iCAFs and IL-10RA\n                      <jats:sup>+<\/jats:sup>\n                      M2 macrophages in tumour tissues. In immune-humanized PDX models, IL-10 blockade with MK-1966 significantly suppressed tumour growth and reduced expression of M2 macrophage markers and proliferation-associated proteins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies an IL-10-dependent iCAF\u2013M2 macrophage immunoregulatory circuit as a central mechanism driving immune suppression in HGSOC. Targeting the IL-10 pathway effectively reverses M2 polarization and suppresses tumour progression, highlighting IL-10 blockade as a promising therapeutic strategy in ovarian cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1790912","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:39:51Z","timestamp":1783661991000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell and spatial profiling reveal an IL-10\u2013associated iCAF\u2013M2 macrophage communication axis in high-grade serous ovarian cancer ascites"],"prefix":"10.3389","volume":"17","author":[{"given":"Ren","family":"Li","sequence":"first","affiliation":[{"name":"The Second Clinical Medical College, Jinan University (Shenzhen People\u2019s Hospital)","place":["Shenzhen, Guangdong, 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Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gynecology, The First Affiliated Hospital of Jinan University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-025-01660-y","article-title":"Global status and attributable risk factors of breast, cervical, ovarian, and 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