2. Academic Validation
  3. AR+TREM2+ macrophage induced pathogenic immunosuppression promotes prostate cancer progression

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

  • Nat Commun. 2025 Jul 29;16(1):6964. doi: 10.1038/s41467-025-62381-x.
Qiaohua Wang # 1,  Yongjian Wu # 2,  Yili Long 1,  Rongna Li 1,  Yu Shi 1,  Yanfen Zheng 1,  Xiaohui Chen 1,  Xiang Li 3,  Yihong Zhou 4,  Xi Huang 5,  Guanmin Jiang 6
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
  • 2 Centre for Infection and Immunity of Guangdong Provincial Engineering Research Centre of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
  • 3 Department of Pathology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
  • 4 Department of Urology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
  • 5 Centre for Infection and Immunity of Guangdong Provincial Engineering Research Centre of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China. huangxi6@mail.sysu.edu.cn.
  • 6 Department of Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China. jianggm3@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 40730555 DOI: 10.1038/s41467-025-62381-x
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.

Figures
Products
Inhibitors & Agonists
Other Products