Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model PMID: 38926596

ADC Targets in Oncology

2026-04-10

Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model

Cancer Gene Ther. 2024 Jun 26. doi: 10.1038/s41417-024-00799-z.

Fei Wang ^# ¹ ² , Shuo Zhang ^# ¹ ³ , Fengjiao Sun ^# ¹ , Weiwei Chen ^# ¹ , Cuilan Liu ¹ , Hongliang Dong ¹ , Bingjie Cui ¹ , Lingyu Li ¹ , Chunlong Sun ⁴ , Wen Du ⁴ , Bin Liu ¹ , Wanfeng Fan ¹ , Jiong Deng ¹ , Clemens A Schmitt ⁵ ⁶ ⁷ ⁸ ⁹ , Xiuwen Wang ¹⁰ , Jing Du ¹¹ ¹²

Affiliations

1. Medical Research Center, Binzhou Medical University Hospital, 256600, Binzhou, PR China.
2. Medical Integration and Practice Center, Qilu Hospital of Shandong University, Shandong University, 250100, Jinan, PR China.
3. Department of Gynecology, Binzhou Medical University Hospital, 256600, Binzhou, PR China.
4. College of Biological and Environmental Engineering, Shandong University of Aeronautics, 256600, Binzhou, PR China.
5. Johannes Kepler University, Altenbergerstraße 69, 4040, Linz, Austria.
6. Department of Hematology and Oncology, Kepler University Hospital, Krankenhausstraße 9, 4020, Linz, Austria.
7. Medical Department of Hematology, Oncology and Tumor Immunology, and Molekulares Krebsforschungszentrum - MKFZ, Campus Virchow Klinikum, Charité-Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353, Berlin, Germany.
8. Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125, Berlin, Germany.
9. Deutsches Konsortium für Translationale Krebsforschung (German Cancer Consortium), Partner Site, Berlin, Germany.
10. Medical Integration and Practice Center, Qilu Hospital of Shandong University, Shandong University, 250100, Jinan, PR China. [email protected].
11. Medical Research Center, Binzhou Medical University Hospital, 256600, Binzhou, PR China. [email protected].
12. Department of Gynecology, Binzhou Medical University Hospital, 256600, Binzhou, PR China. [email protected].
# Contributed equally.

Abstract

Glioblastoma (GBM) is the most common and aggressive primary brain cancer; angiogenesis and immunosuppression exacerbate GBM progression. COUP-TFII demonstrates pro-angiogenesis activity; however, its role in glioma progression remains unclear. This study revealed that COUP-TFII promotes angiogenesis in gliomas by inducing transdifferentiation of glioma cells into endothelial-like cells. Mechanistic investigation suggested that COUP-TFII as a transcription factor exerts its function via binding to the promoter of TXNIP. Interestingly, COUP-TFII knockdown attenuated tumorigenesis and tumor progression in an immunocompetent mouse model but promoted tumor progression in an immuno-deficient mouse model. As an explanation, repression of COUP-TFII induces cellular senescence and activates immune surveillance in glioma cells in vitro and in vivo. In addition, we used heparin-polyethyleneimine (HPEI) nanoparticles to deliver COUP-TFII shRNA, which regulated tumor angiogenesis and immunosuppression in an in situ GBM mouse model. This study provides a novel strategy and potential therapeutic targets to treat GBM.