Bibliographic Details
| Title: |
Clofazimine enhances anti-PD-1 immunotherapy in glioblastoma by inhibiting Wnt6 signaling and modulating the tumor immune microenvironment |
| Authors: |
Yuze Zhao, Yuguang Song, Weiping Li, Jiangping Wu, Zhengbao Zhao, Tingli Qu, Hong Xiao, Manyuan Wang, Min Zhu, Peiming Zheng, Huili Wan, Qingkun Song, Huixia Zheng, Shuo Wang |
| Source: |
Cancer Immunology, Immunotherapy, Vol 74, Iss 4, Pp 1-17 (2025) |
| Publisher Information: |
Springer, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Clofazimine, Anti-PD-1 immunotherapy, Glioblastoma, Wnt6 signaling pathway, Tumor immune microenvironment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Abstract Glioblastoma multiforme (GBM) is an aggressive and lethal primary brain tumor with limitedtreatment options due to its resistance to conventional therapies and an immunosuppressive tumor microenvironment. In this study, we investigated whether clofazimine, an inhibitor of the Wnt/β-catenin signaling pathway, could enhance the efficacy of anti-PD-1 immunotherapy in GBM. Our in vitro and in vivo experiments demonstrated that clofazimine suppressed GBM cell proliferation, induced apoptosis, and inhibited invasion by downregulating Wnt6-mediated activation of the Wnt/β-catenin pathway and the downstream MEK/ERK signaling cascade, leading to decreased PD-L1 expression. Notably, the combination of clofazimine and anti-PD-1 therapy significantly reduced tumor growth and intracranial invasion in orthotopic GBM mouse models, resulting in extended survival. This combination therapy also reshaped the tumor immune microenvironment by increasing cytotoxic CD8+ T cell infiltration, reducing regulatory T cells, and promoting T cell receptor clonality and diversity, indicative of a robust anti-tumor immune response. Our findings suggest that clofazimine enhances the therapeutic effects of anti-PD-1 immunotherapy in GBM through modulation of the Wnt6/β-catenin/PD-L1 axis and reshaping the immune microenvironment. While these results are promising, further clinical studies are needed to evaluate the efficacy and safety of this combinatory approach in GBM patients. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1432-0851 |
| Relation: |
https://doaj.org/toc/1432-0851 |
| DOI: |
10.1007/s00262-025-03994-5 |
| Access URL: |
https://doaj.org/article/6d9f212a77ef49d9a424694ccb250144 |
| Accession Number: |
edsdoj.6d9f212a77ef49d9a424694ccb250144 |
| Database: |
Directory of Open Access Journals |
Full Text from SpringerLink