WNT11 Promotes immune evasion and resistance to Anti-PD-1 therapy in liver metastasis

Weiliang Jiang, Bingjie Guan, Hongcheng Sun, Yushuai Mi, Sanjun Cai, Rong Wan, Xinxiang Li, Peng Lian, Dawei Li () and Senlin Zhao ()
Additional contact information
Weiliang Jiang: No. 270 Dong’an Road
Bingjie Guan: No. 650 New Songjiang Road
Hongcheng Sun: No. 650 New Songjiang Road
Yushuai Mi: No. 247 Beiyuan Road
Sanjun Cai: No. 270 Dong’an Road
Rong Wan: No. 100 Haining Road
Xinxiang Li: No. 270 Dong’an Road
Peng Lian: No. 270 Dong’an Road
Dawei Li: No. 270 Dong’an Road
Senlin Zhao: No. 270 Dong’an Road

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Liver metastasis (LM) poses a significant challenge in cancer treatment, with limited available therapeutic options and poor prognosis. Understanding the dynamics of tumor microenvironment (TME) and immune interactions is crucial for developing effective treatments. We find that WNT11 promoted CD8+ T-cell exclusion and suppression, which was correlated with poor prognosis in LM. Mechanistically, WNT11-overexpressing tumor cells directly reduce CD8+ T-cell recruitment and activity by decreasing CXCL10 and CCL4 expression through CAMKII-mediated β-catenin/AFF3 downregulation. WNT11-overexpressing tumor cells promote immunosuppressive macrophage polarization by inducing IL17D expression via the CAMKII/NF-κB pathway, which result in CD8+ T-cell suppression. Moreover, CAMKII inhibition increases the efficacy of anti-PD-1 therapy in mouse model of LM. Serum expression of WNT11 is identified as a potential minimally invasive biomarker in the management of colorectal cancer-LM with immunotherapy. Our findings highlight WNT11/CAMKII axis as a critical regulator of the TME and a promising target for immunotherapy in patients with LM.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56714-z 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_s41467-025-56714-z

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

DOI: 10.1038/s41467-025-56714-z

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 ().