Inhibition of ICAM1 diminishes stemness and enhances antitumor immunity in glioblastoma via β-catenin/PD-L1 signaling.

ABSTRACT: Glioblastoma (GBM) stem cells (GSCs) are pivotal in tumor initiation, recurrence, and therapeutic resistance, underscoring their critical role in the complex pathology of GBM. Despite their recognized importance, the mechanisms by which GSCs facilitate immune evasion, especially in emerging immunotherapies, remain incompletely understood. Here, we identify intercellular adhesion molecule 1 (ICAM1) as a key regulator of GSC stemness and tumorigenicity, promoting an immunosuppressive microenvironment via β-catenin/PD-L1 signaling. Mechanistically, ICAM1 interacts with ZNRF3, leading to its autoubiquitination and clearance, stabilizing LRP6, and activating β-catenin signaling, which upregulates PD-L1 expression. Combined treatment with anti-ICAM1 and anti-PD-1 antibodies results in the most e

SUBMITTER: Guo M 

PROVIDER: S-EPMC12484827 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature