Clofazimine enhances anti-PD-1 immunotherapy in glioblastoma by inhibiting Wnt6 signaling and modulating the tumor immune microenvironment

Cancer Immunology Immunotherapy, Год журнала: 2025, Номер 74(4)

Опубликована: Март 7, 2025

Glioblastoma multiforme (GBM) is an aggressive and lethal primary brain tumor with limitedtreatment options due to its resistance conventional therapies immunosuppressive microenvironment. In this study, we investigated whether clofazimine, inhibitor of the Wnt/β-catenin signaling pathway, could enhance efficacy anti-PD-1 immunotherapy in GBM. Our vitro vivo experiments demonstrated that clofazimine suppressed GBM cell proliferation, induced apoptosis, inhibited invasion by downregulating Wnt6-mediated activation pathway downstream MEK/ERK cascade, leading decreased PD-L1 expression. Notably, combination therapy significantly reduced growth intracranial orthotopic mouse models, resulting extended survival. This also reshaped immune microenvironment increasing cytotoxic CD8+ T infiltration, reducing regulatory cells, promoting receptor clonality diversity, indicative a robust anti-tumor response. findings suggest enhances therapeutic effects through modulation Wnt6/β-catenin/PD-L1 axis reshaping While these results are promising, further clinical studies needed evaluate safety combinatory approach patients.

Язык: Английский

Targeting VEGF signaling for tumor microenvironment remodeling and metastasis inhibition: Therapeutic strategies and insights

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 186, С. 118023 - 118023

Опубликована: Апрель 2, 2025

Язык: Английский

The multifaceted modulation of mitochondrial metabolism in tumorigenesis

Mitochondrion, Год журнала: 2024, Номер 80, С. 101977 - 101977

Опубликована: Ноя. 4, 2024

Язык: Английский