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

Qiaohua Wang, Yongjian Wu, Yili Long, Rongna Li, Yu Shi, Yanfen Zheng, Xiaohui Chen, Xiang Li, Yihong Zhou, Xi Huang () and Guanmin Jiang ()
Additional contact information
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

Nature Communications, 2025, vol. 16, issue 1, 1-23

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62381-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62381-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62381-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().