Wnt inhibition alleviates resistance to anti-PD1 therapy and improves antitumor immunity in glioblastoma.

ABSTRACT: Wnt signaling plays a crucial role for many developmental processes. It is also pivotal in the generation and limited treatment outcomes of glioblastoma (GBM). Here, we identified Wnt7b, which is markedly upregulated in GBM patients, as a determinant of resistance to immune checkpoint blockers (αPD1; anti-Programmed Cell Death Protein 1) in a clinically relevant, αPD1-resistant GBM murine model with abundant stem cells. We observed that increased levels of Wnt7b and β-catenin correlated with the resistance to αPD1. Treatment combining a porcupine inhibitor WNT974 with αPD1 reprogrammed the immune suppressive tumor microenvironment (TME) to bolster antitumor immune responses and extended the survival of mice bearing orthotopic GBM, with 25% long-term survivors. Our causal studies revealed t

SUBMITTER: Krishnan S 

PROVIDER: S-EPMC12478157 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature