{ "abstract": "Tumor-associated macrophages (TAMs) in glioblastoma (GBM) often adopt tumor-supportive phenotypes, but the underlying signaling in TAMs is unclear. Interleukin-10 (IL-10) is frequently upregulated in tumors, but the understanding of IL-10 in the tumor immune microenvironment is controversial. This study aims to determine the roles of IL-10 receptor alpha (IL-10Rα) signaling in TAMs and explore the targetable mediators for GBM treatment. We found that growth of intracranial GBMs was delayed in engineered mice with myeloid-specific knock-out of IL-10Rα, which was accompanied by changes in TAM phenotypes. Meanwhile, IL-10 expression in GBMs, which was largely accredited to TAMs, were not affected by IL-10Rα deficiency. RNA-sequencing analysis and immunostaining revealed cyclooxygenases COX-1/2 as potential downstream effectors of IL-10Rα in TAMs. Pharmacological inhibition of COX-1/2 suppressed bone-marrow derived macrophages (BMDM) polarization upon IL-4/IL-10 treatment. Consistently, the COX inhibitor NS-398 mitigated intracranial GBM growth. In summary, we not only demonstrated the crucial roles of IL-10Rα but also discovered COX-1/2 as downstream targets for pro-tumor phenotypes of TAMs in GBMs. These findings provide new clues for future development of immunotherapies for GBM treatment.", "abstract_shown": true, "affiliations": [ "Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.", "Intelligent Pathology Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.", "Department of Medical Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.", "Henan Key Laboratory of Genetic and Developmental Disorders, Institute of Children's Health, Henan Academy of Innovations in Medical Sciences, Zhengzhou, China.", "Zhengzhou Hospital of Beijing Children's Hospital, Zhengzhou, China.", "Department of Cell Biology, School of Life Science, Anhui Medical University, Hefei, China. ailizhang829@163.com.", "Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. ailizhang829@163.com.", "School of Basic Medical Sciences, Anhui Medical University, Hefei, China. ailizhang829@163.com.", "Department of Medical Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. libf@ustc.edu.cn.", "Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. WZAZ@ustc.edu.cn.", "Intelligent Pathology Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. WZAZ@ustc.edu.cn.", "Henan Key Laboratory of Genetic and Developmental Disorders, Institute of Children's Health, Henan Academy of Innovations in Medical Sciences, Zhengzhou, China. WZAZ@ustc.edu.cn.", "Zhengzhou Hospital of Beijing Children's Hospital, Zhengzhou, China. WZAZ@ustc.edu.cn." ], "article_type": "research article", "arxiv": null, "author_total": 12, "authors": [ { "affs": [ 0, 1 ], "name": "Jiahui Zhou" }, { "affs": [ 0, 1 ], "name": "Bingxi Shi" }, { "affs": [ 2 ], "name": "Qiangsheng Li" }, { "affs": [ 0, 1 ], "name": "Fangzhen Li" }, { "affs": [ 0, 1 ], "name": "Zhiwen Zhang" }, { "affs": [ 0, 1 ], "name": "Qiuhong Zhu" }, { "affs": [ 3, 4 ], "name": "Huipeng Wang" }, { "affs": [ 0, 1 ], "name": "Wei Wang", "orcid": "0000-0002-2000-3255" }, { "affs": [ 0, 1 ], "name": "Hai-Bo Wu", "orcid": "0000-0003-0817-9191" }, { "affs": [ 5, 6, 7 ], "name": "Aili Zhang", "orcid": "0000-0002-3494-5534" }, { "affs": [ 8 ], "name": "Bofeng Li", "orcid": "0000-0002-9110-8804" }, { "affs": [ 9, 10, 11, 12 ], "name": "Wenchao Zhou", "orcid": "0000-0002-6650-1831" } ], "bibtex": "https://research.draconitic.com/paper/443jy49knjnnk.bib", "cited_by": 0, "doi": "10.1038/s41419-026-09072-7", "fulltext_url": "https://europepmc.org/articles/PMC13686974", "id": "443jy49knjnnk", "issns": [ "2041-4889" ], "landing_url": "https://europepmc.org/article/MED/42907461", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "QH573-671" ], [ "openalex", "2403|Immune cells in cancer" ] ], "openalex": "W7171302469", "pdf_url": "https://europepmc.org/articles/PMC13686974?pdf=render", "pmcid": "PMC13686974", "pmid": "42907461", "published": "2026-07-01", "publisher": "Nature Publishing Group", "ris": "https://research.draconitic.com/paper/443jy49knjnnk.ris", "sources": [ { "first_seen": "2026-10-30T12:19:57Z", "native_id": "MED:42907461", "source": "europepmc", "url": "https://europepmc.org/article/MED/42907461" }, { "first_seen": "2026-10-30T13:46:30Z", "native_id": "0cc99b02ba16421b8428c7c90d9471b9", "source": "doaj", "url": "https://doi.org/10.1038/s41419-026-09072-7" } ], "subjects": [ { "field": "biology", "origin": "openalex:2403|Immune cells in cancer", "subfield": "immunology" } ], "title": "Cyclooxygenase-mediated IL-10Rα signaling underlies pro-tumor phenotypes of macrophages in glioma.", "title_text": "Cyclooxygenase-mediated IL-10Rα signaling underlies pro-tumor phenotypes of macrophages in glioma.", "type": "peer-reviewed", "updated_at": "2026-10-31T14:20:51Z", "url": "https://research.draconitic.com/paper/443jy49knjnnk", "venue": "Cell death & disease", "versions": [] }