Enhancing T cell infiltration in glioblastoma: a review article on challenges and therapeutic strategies

Cancer Treat Res Commun. 2025:45:100999. doi: 10.1016/j.ctarc.2025.100999. Epub 2025 Sep 9.

Abstract

This review focuses on enhancing T-cell infiltration in glioblastoma (GBM) while overcoming its immunosuppressive tumor microenvironment (TME). Key strategies include targeting myeloid-derived suppressor cells (MDSCs) to reduce immunosuppression and repolarizing tumor-associated macrophages (TAMs) from an M2 (immunosuppressive) phenotype to an M1 (proinflammatory) phenotype to increase T-cell function. Administering chemokines can help attract more effector T cells to the tumor site. Combining immune checkpoint inhibitors (ICIs) with other treatments can further increase T cell activity. To make immunotherapy more effective in GBM, it is also essential to address the immunosuppressive signals in the TME, such as transforming growth factor beta (TGF-β) and interleukin-10 (IL-10).

Keywords: Blood–brain barrier; CAR-T cell; Glioblastoma; Immunosuppressive microenvironment; Immunotherapy; Tumor microenvironment; Tumor-infiltrating lymphocytes.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / immunology
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / therapy
  • Glioblastoma* / drug therapy
  • Glioblastoma* / immunology
  • Glioblastoma* / pathology
  • Glioblastoma* / therapy
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / methods
  • Lymphocytes, Tumor-Infiltrating* / drug effects
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Myeloid-Derived Suppressor Cells / drug effects
  • Myeloid-Derived Suppressor Cells / immunology
  • T-Lymphocytes* / drug effects
  • T-Lymphocytes* / immunology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Immune Checkpoint Inhibitors