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

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 o

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC11889303 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature