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Peer-reviewedCC BYCell death & disease

Cyclooxygenase-mediated IL-10Rα signaling underlies pro-tumor phenotypes of macrophages in glioma.

  • Jiahui Zhou1,2
  • Bingxi Shi1,2
  • Qiangsheng Li3
  • Fangzhen Li1,2
  • Zhiwen Zhang1,2
  • Qiuhong Zhu1,2
  • Huipeng Wang4,5
  • Wei Wang1,2
  • Hai-Bo Wu1,2
  • Aili Zhang6,7,8
  • Bofeng Li9
  • Wenchao Zhou10,11,12,13
13 affiliations
  1. 1Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  2. 2Intelligent Pathology Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  3. 3Department of Medical Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  4. 4Henan Key Laboratory of Genetic and Developmental Disorders, Institute of Children's Health, Henan Academy of Innovations in Medical Sciences, Zhengzhou, China.
  5. 5Zhengzhou Hospital of Beijing Children's Hospital, Zhengzhou, China.
  6. 6Department of Cell Biology, School of Life Science, Anhui Medical University, Hefei, China. [email protected].
  7. 7Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. [email protected].
  8. 8School of Basic Medical Sciences, Anhui Medical University, Hefei, China. [email protected].
  9. 9Department of Medical Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. [email protected].
  10. 10Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. [email protected].
  11. 11Intelligent Pathology Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. [email protected].
  12. 12Henan Key Laboratory of Genetic and Developmental Disorders, Institute of Children's Health, Henan Academy of Innovations in Medical Sciences, Zhengzhou, China. [email protected].
  13. 13Zhengzhou Hospital of Beijing Children's Hospital, Zhengzhou, China. [email protected].
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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.

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Cite

BibTeXRIS
BibTeX
@article{zhou2026cyclooxygenasemediated,
  title = {{Cyclooxygenase-mediated IL-10Rα signaling underlies pro-tumor phenotypes of macrophages in glioma.}},
  author = {Jiahui Zhou and Bingxi Shi and Qiangsheng Li and Fangzhen Li and Zhiwen Zhang and Qiuhong Zhu and Huipeng Wang and Wei Wang and Hai-Bo Wu and Aili Zhang and Bofeng Li and Wenchao Zhou},
  journal = {Cell death \& disease},
  year = {2026},
  month = jul,
  doi = {10.1038/s41419-026-09072-7},
  url = {https://europepmc.org/article/MED/42907461},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cyclooxygenase-mediated IL-10Rα signaling underlies pro-tumor phenotypes of macrophages in glioma.
AU  - Jiahui Zhou
AU  - Bingxi Shi
AU  - Qiangsheng Li
AU  - Fangzhen Li
AU  - Zhiwen Zhang
AU  - Qiuhong Zhu
AU  - Huipeng Wang
AU  - Wei Wang
AU  - Hai-Bo Wu
AU  - Aili Zhang
AU  - Bofeng Li
AU  - Wenchao Zhou
PY  - 2026
DA  - 2026/07/01
JO  - Cell death & disease
DO  - 10.1038/s41419-026-09072-7
UR  - https://europepmc.org/article/MED/42907461
AB  - 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.
SN  - 2041-4889
ER  -