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  3. Glioma cells produce soluble PD-L1 via the Wnt/β-catenin signaling pathway to suppress CD8+ T cell activity

Glioma cells produce soluble PD-L1 via the Wnt/β-catenin signaling pathway to suppress CD8+ T cell activity

  • Biochim Biophys Acta Mol Basis Dis. 2025 Aug 8;1871(8):168013. doi: 10.1016/j.bbadis.2025.168013.
Zihan Zhou 1,  Yao Wang 1,  Ying Wang 1,  Chunhui Yuan 2,  Junjian Lin 1,  Xinbin Bai 3,  Yunhao Chen 2,  Man Hu 4,  Xingchen Ding 5
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
  • 2 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • 3 Department of Oncology, Jining Tumor Hospital, Jining, Shandong, China.
  • 4 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: human5770@163.com.
  • 5 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: SDdingxingchen@126.com.
PMID: 40784599 DOI: 10.1016/j.bbadis.2025.168013
Abstract

Soluble programmed death ligand 1 (sPD-L1) is emerging as a novel prognostic marker, potentially replacing PD-L1 for assessing prognosis and immunotherapy effectiveness. However, little is known about sPD-L1. This study aimed to assess sPD-L1's potential as a biomarker and explore its origin and biological function. The study found sPD-L1 concentration in plasma is linked to worse overall survival (OS) in glioma. Patients with high Ki-67 expression, IDH-wild type or high-grade have higher level of sPD-L1. Notably, sPD-L1 concentration is positive correlations with tumor volume in patients and mice. Mice plasma with varying sPD-L1 concentration was co-cultured with CD8+ T cells to investigate sPD-L1 activity and function. We conclude that glioma cells produce sPD-L1 through the Wnt/β-catenin signaling pathway, which interacts with the PD-1 receptor on CD8+ T cells, inhibiting their function by reducing IFN-γ levels. Wnt inhibitors combined with PD-L1 inhibitors can enhance the anti-tumor effect by further reducing sPD-L1 levels.

Keywords

Glioma; Soluble PD-L1; Wnt inhibitor.

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