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AR+TREM2+ macrophage induced pathogenic immunosuppression promotes prostate cancer progression

Author

Listed:
  • Qiaohua Wang

    (Sun Yat-sen University)

  • Yongjian Wu

    (Sun Yat-sen University)

  • Yili Long

    (Sun Yat-sen University)

  • Rongna Li

    (Sun Yat-sen University)

  • Yu Shi

    (Sun Yat-sen University)

  • Yanfen Zheng

    (Sun Yat-sen University)

  • Xiaohui Chen

    (Sun Yat-sen University)

  • Xiang Li

    (Sun Yat-sen University)

  • Yihong Zhou

    (Sun Yat-sen University)

  • Xi Huang

    (Sun Yat-sen University)

  • Guanmin Jiang

    (Sun Yat-sen University)

Abstract

The androgen receptor (AR) usually drives prostate cancer cell growth, yet its role in immune cells such as tumour-associated macrophages (TAMs), remains unclear. We find that macrophages co-expressing AR and triggering receptor expressed on myeloid cells-2 (TREM2) exhibiting potent immunosuppressive and tumour-promoting effects. Genetic ablation of TREM2 combined with pharmacological blockade of AR, significantly reduces tumour progression in prostate cancer mouse models. Mechanistically, apolipoprotein E (APOE) in tumour microenvironment (TME) binds to TREM2 on macrophages and promotes AR expression. AR further upregulates transcription expression of Il10, Tgfb1, Il23a, and Ccl2 in macrophages. AR, TREM2, and APOE expression increases in prostate cancer patients and correlates with poor prognosis. In conclusion, these findings indicate an alternative mechanism of tumour immune evasion, supporting the development of immunomodulatory agents targeting AR and TREM2 in TAMs to delay or reverse endocrine therapy resistance or immune checkpoint therapy resistance in prostate cancer.

Suggested Citation

  • Qiaohua Wang & Yongjian Wu & Yili Long & Rongna Li & Yu Shi & Yanfen Zheng & Xiaohui Chen & Xiang Li & Yihong Zhou & Xi Huang & Guanmin Jiang, 2025. "AR+TREM2+ macrophage induced pathogenic immunosuppression promotes prostate cancer progression," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62381-x
    DOI: 10.1038/s41467-025-62381-x
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