Beyond Passive Bystander: Glioblastoma-Educated Astrocyte Suppressing T Cell

Front Biosci (Landmark Ed). 2025 Oct 31;30(10):44810. doi: 10.31083/FBL44810.

Abstract

Faust Akl et al. revealed in Nature a paradigm-shifting mechanism distinct from myeloid-driven immunosuppression, whereby glioblastoma induces T-cell apoptosis via tumor-derived IL-11, prompting astrocytes to reprogram into immunosuppressive tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)+ effectors, thereby establishing astrocytes as active immunomodulators. Therapeutically, herpes simplex virus type 1 (HSV-1) (anti-TRAIL) achieves a dual therapeutic effect, offering novel strategies to overcome glioblastoma (GBM)'s evasion tactics.

Keywords: IL-11; STAT3; astrocyte; glioblastoma; immune-suppressive TME; oncolytic virus.

MeSH terms

  • Animals
  • Apoptosis
  • Astrocytes* / immunology
  • Brain Neoplasms* / immunology
  • Brain Neoplasms* / therapy
  • Glioblastoma* / immunology
  • Glioblastoma* / pathology
  • Glioblastoma* / therapy
  • Herpesvirus 1, Human
  • Humans
  • T-Lymphocytes* / immunology
  • TNF-Related Apoptosis-Inducing Ligand / immunology
  • TNF-Related Apoptosis-Inducing Ligand / metabolism

Substances

  • TNF-Related Apoptosis-Inducing Ligand